Metal nanoparticles caused death of metastatic MDA-MB-231 breast cancer cells:
- Adeyemi, Oluyomi, Edkins, Adrienne L, Whiteley, Christopher
- Authors: Adeyemi, Oluyomi , Edkins, Adrienne L , Whiteley, Christopher
- Date: 2013
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164797 , vital:41173 , DOI: 10.1016/j.toxlet.2013.05.599
- Description: Available data on the toxicity of nanoparticles is a subject of controversy. The interaction of nanoparticles with biological systems including living cells has become one of the most urgent areas of collaborative research in materials science and biology. This is due to the fact that toxicity of nanomaterials are ill defined in terms of cause–effect relationships.
- Full Text:
- Date Issued: 2013
- Authors: Adeyemi, Oluyomi , Edkins, Adrienne L , Whiteley, Christopher
- Date: 2013
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164797 , vital:41173 , DOI: 10.1016/j.toxlet.2013.05.599
- Description: Available data on the toxicity of nanoparticles is a subject of controversy. The interaction of nanoparticles with biological systems including living cells has become one of the most urgent areas of collaborative research in materials science and biology. This is due to the fact that toxicity of nanomaterials are ill defined in terms of cause–effect relationships.
- Full Text:
- Date Issued: 2013
Theiler’s murine encephalomyelitis virus infection induces a redistribution of heat shock proteins 70 and 90 in BHK-21 cells, and is inhibited by novobiocin and geldanamycin:
- Mutsvunguma, Lorraine Z, Moetlhoa, Boitumelo, Edkins, Adrienne L, Luke, Garry A, Blatch, Gregory L, Knox, Caroline M
- Authors: Mutsvunguma, Lorraine Z , Moetlhoa, Boitumelo , Edkins, Adrienne L , Luke, Garry A , Blatch, Gregory L , Knox, Caroline M
- Date: 2011
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165085 , vital:41207 , DOI: 10.1007/s12192-011-0262-x
- Description: Theiler’s murine encephalomyelitis virus (TMEV) is a positive-sense RNA virus belonging to the Cardiovirus genus in the family Picornaviridae. In addition to other host cellular factors and pathways, picornaviruses utilise heat shock proteins (Hsps) to facilitate their propagation in cells. This study investigated the localisation of Hsps 70 and 90 in TMEV-infected BHK-21 cells by indirect immunofluorescence and confocal microscopy. The effect of Hsp90 inhibitors novobiocin (Nov) and geldanamycin (GA) on the development of cytopathic effect (CPE) induced by infection was also examined. Hsp90 staining was uniformly distributed in the cytoplasm of uninfected cells but was found concentrated in the perinuclear region during late infection where it overlapped with the signal for non-structural protein 2C within the viral replication complex.
- Full Text:
- Date Issued: 2011
- Authors: Mutsvunguma, Lorraine Z , Moetlhoa, Boitumelo , Edkins, Adrienne L , Luke, Garry A , Blatch, Gregory L , Knox, Caroline M
- Date: 2011
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165085 , vital:41207 , DOI: 10.1007/s12192-011-0262-x
- Description: Theiler’s murine encephalomyelitis virus (TMEV) is a positive-sense RNA virus belonging to the Cardiovirus genus in the family Picornaviridae. In addition to other host cellular factors and pathways, picornaviruses utilise heat shock proteins (Hsps) to facilitate their propagation in cells. This study investigated the localisation of Hsps 70 and 90 in TMEV-infected BHK-21 cells by indirect immunofluorescence and confocal microscopy. The effect of Hsp90 inhibitors novobiocin (Nov) and geldanamycin (GA) on the development of cytopathic effect (CPE) induced by infection was also examined. Hsp90 staining was uniformly distributed in the cytoplasm of uninfected cells but was found concentrated in the perinuclear region during late infection where it overlapped with the signal for non-structural protein 2C within the viral replication complex.
- Full Text:
- Date Issued: 2011
Reaction of Perrhenate with Phthalocyanine Derivatives in the Presence of Reducing Agents and Rhenium Oxide Nanoparticles in Biomedical Applications
- Ntsimango, Songeziwe, Gandidzanwa, Sendibitiyosi, Joseph, Sinelizwi V, Hosten, Eric C, Randall, Marvin, Edkins, Adrienne L, Khene, Samson M, Mashazi, Philani N, Nyokong, Tebello, Abrahams, Abubak’r, Tshentu, Zenixole R
- Authors: Ntsimango, Songeziwe , Gandidzanwa, Sendibitiyosi , Joseph, Sinelizwi V , Hosten, Eric C , Randall, Marvin , Edkins, Adrienne L , Khene, Samson M , Mashazi, Philani N , Nyokong, Tebello , Abrahams, Abubak’r , Tshentu, Zenixole R
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/300257 , vital:57910 , xlink:href="https://doi.org/10.1002/open.202200037"
- Description: A novel alternative route to access rhenium(V)−phthalocyanine complexes through direct metalation of metal-free phthalocyanines (H2Pcs) with a rhenium(VII) salt in the presence of various two-electron reducing agents is presented. Direct ion metalation of tetraamino- or tetranitrophthalocyanine with perrhenate (ReO4−) in the presence of triphenylphosphine led to oxidative decomposition of the H2Pcs, giving their respective phthalonitriles. Conversely, treatment of H2Pcs with ReO4− employing sodium metabisulfite yielded the desired ReVO−Pc complex. Finally, reaction of H2Pcs with ReO4− and NaBH4 as reducing agent led to the formation of rhenium oxide (RexOy) nanoparticles (NPs). The NP synthesis was optimised, and the RexOy NPs were capped with folic acid (FA) conjugated with tetraaminophthalocyanine (TAPc) to enhance their cancer cell targeting ability. The cytotoxicity profile of the resultant RexOy−TAPc−FA NPs was assessed and found to be greater than 80 % viability in four cell lines, namely, MDA−MB-231, HCC7, HCC1806 and HEK293T. Non-cytotoxic concentrations were determined and employed in cancer cell localization studies. The particle size effect on localization of NPs was also investigated using confocal fluorescence and transmission electron microscopy. The smaller NPs (≈10 nm) were found to exhibit stronger fluorescence properties than the ≈50 nm NPs and exhibited better cell localization ability than the ≈50 nm NPs.
- Full Text:
- Date Issued: 2022
- Authors: Ntsimango, Songeziwe , Gandidzanwa, Sendibitiyosi , Joseph, Sinelizwi V , Hosten, Eric C , Randall, Marvin , Edkins, Adrienne L , Khene, Samson M , Mashazi, Philani N , Nyokong, Tebello , Abrahams, Abubak’r , Tshentu, Zenixole R
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/300257 , vital:57910 , xlink:href="https://doi.org/10.1002/open.202200037"
- Description: A novel alternative route to access rhenium(V)−phthalocyanine complexes through direct metalation of metal-free phthalocyanines (H2Pcs) with a rhenium(VII) salt in the presence of various two-electron reducing agents is presented. Direct ion metalation of tetraamino- or tetranitrophthalocyanine with perrhenate (ReO4−) in the presence of triphenylphosphine led to oxidative decomposition of the H2Pcs, giving their respective phthalonitriles. Conversely, treatment of H2Pcs with ReO4− employing sodium metabisulfite yielded the desired ReVO−Pc complex. Finally, reaction of H2Pcs with ReO4− and NaBH4 as reducing agent led to the formation of rhenium oxide (RexOy) nanoparticles (NPs). The NP synthesis was optimised, and the RexOy NPs were capped with folic acid (FA) conjugated with tetraaminophthalocyanine (TAPc) to enhance their cancer cell targeting ability. The cytotoxicity profile of the resultant RexOy−TAPc−FA NPs was assessed and found to be greater than 80 % viability in four cell lines, namely, MDA−MB-231, HCC7, HCC1806 and HEK293T. Non-cytotoxic concentrations were determined and employed in cancer cell localization studies. The particle size effect on localization of NPs was also investigated using confocal fluorescence and transmission electron microscopy. The smaller NPs (≈10 nm) were found to exhibit stronger fluorescence properties than the ≈50 nm NPs and exhibited better cell localization ability than the ≈50 nm NPs.
- Full Text:
- Date Issued: 2022
Fibronectin is a stress responsive gene regulated by HSF1 in response to geldanamycin
- Dhanani, Karim C H, Samson, William J, Edkins, Adrienne L
- Authors: Dhanani, Karim C H , Samson, William J , Edkins, Adrienne L
- Date: 2017
- Language: English
- Type: article , text
- Identifier: http://hdl.handle.net/10962/59931 , vital:27711 , https://doi:10.1038/s41598-017-18061-y
- Description: Fibronectin is an extracellular matrix glycoprotein with key roles in cell adhesion and migration. Hsp90 binds directly to fibronectin and Hsp90 depletion regulates fibronectin matrix stability. Where inhibition of Hsp90 with a C-terminal inhibitor, novobiocin, reduced the fibronectin matrix, treatment with an N-terminal inhibitor, geldanamycin, increased fibronectin levels. Geldanamycin treatment induced a stress response and a strong dose and time dependent increase in fibronectin mRNA via activation of the fibronectin promoter. Three putative heat shock elements (HSEs) were identified in the fibronectin promoter. Loss of two of these HSEs reduced both basal and geldanamycin-induced promoter activity, as did inhibition of the stress-responsive transcription factor HSF1. Binding of HSF1 to one of the putative HSE was confirmed by ChIP under basal conditions, and occupancy shown to increase with geldanamycin treatment. These data support the hypothesis that fibronectin is stress-responsive and a functional HSF1 target gene. COLA42 and LAMB3 mRNA levels were also increased with geldanamycin indicating that regulation of extracellular matrix (ECM) genes by HSF1 may be a wider phenomenon. Taken together, these data have implications for our understanding of ECM dynamics in stress-related diseases in which HSF1 is activated, and where the clinical application of N-terminal Hsp90 inhibitors is intended.
- Full Text:
- Date Issued: 2017
- Authors: Dhanani, Karim C H , Samson, William J , Edkins, Adrienne L
- Date: 2017
- Language: English
- Type: article , text
- Identifier: http://hdl.handle.net/10962/59931 , vital:27711 , https://doi:10.1038/s41598-017-18061-y
- Description: Fibronectin is an extracellular matrix glycoprotein with key roles in cell adhesion and migration. Hsp90 binds directly to fibronectin and Hsp90 depletion regulates fibronectin matrix stability. Where inhibition of Hsp90 with a C-terminal inhibitor, novobiocin, reduced the fibronectin matrix, treatment with an N-terminal inhibitor, geldanamycin, increased fibronectin levels. Geldanamycin treatment induced a stress response and a strong dose and time dependent increase in fibronectin mRNA via activation of the fibronectin promoter. Three putative heat shock elements (HSEs) were identified in the fibronectin promoter. Loss of two of these HSEs reduced both basal and geldanamycin-induced promoter activity, as did inhibition of the stress-responsive transcription factor HSF1. Binding of HSF1 to one of the putative HSE was confirmed by ChIP under basal conditions, and occupancy shown to increase with geldanamycin treatment. These data support the hypothesis that fibronectin is stress-responsive and a functional HSF1 target gene. COLA42 and LAMB3 mRNA levels were also increased with geldanamycin indicating that regulation of extracellular matrix (ECM) genes by HSF1 may be a wider phenomenon. Taken together, these data have implications for our understanding of ECM dynamics in stress-related diseases in which HSF1 is activated, and where the clinical application of N-terminal Hsp90 inhibitors is intended.
- Full Text:
- Date Issued: 2017
The palladacycle, AJ-5, exhibits anti-tumour and anti-cancer stem cell activity in breast cancer cells:
- Aliwaini, Saeb, Peres, Jade, Kröger, Wendy L, Blanckenberg, Angelique, de la Mare, Jo-Anne, Edkins, Adrienne L, Mapolie, Selwyn, Prince, Sharon
- Authors: Aliwaini, Saeb , Peres, Jade , Kröger, Wendy L , Blanckenberg, Angelique , de la Mare, Jo-Anne , Edkins, Adrienne L , Mapolie, Selwyn , Prince, Sharon
- Date: 2015
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164874 , vital:41180 , DOI: 10.1016/j.canlet.2014.11.027
- Description: Breast cancer is the most common malignancy amongst women worldwide but despite enormous efforts to address this problem, there is still limited success with most of the current therapeutic strategies. The current study describes the anti-cancer activity of a binuclear palladacycle complex (AJ-5) in oestrogen receptor positive (MCF7) and oestrogen receptor negative (MDA-MB-231) breast cancer cells as well as human breast cancer stem cells. AJ-5 is shown to induce DNA double strand breaks leading to intrinsic and extrinsic apoptosis and autophagy cell death pathways which are mediated by the p38 MAP kinase. This study provides evidence that AJ-5 is potentially an effective compound in the treatment of breast cancer.
- Full Text:
- Date Issued: 2015
- Authors: Aliwaini, Saeb , Peres, Jade , Kröger, Wendy L , Blanckenberg, Angelique , de la Mare, Jo-Anne , Edkins, Adrienne L , Mapolie, Selwyn , Prince, Sharon
- Date: 2015
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164874 , vital:41180 , DOI: 10.1016/j.canlet.2014.11.027
- Description: Breast cancer is the most common malignancy amongst women worldwide but despite enormous efforts to address this problem, there is still limited success with most of the current therapeutic strategies. The current study describes the anti-cancer activity of a binuclear palladacycle complex (AJ-5) in oestrogen receptor positive (MCF7) and oestrogen receptor negative (MDA-MB-231) breast cancer cells as well as human breast cancer stem cells. AJ-5 is shown to induce DNA double strand breaks leading to intrinsic and extrinsic apoptosis and autophagy cell death pathways which are mediated by the p38 MAP kinase. This study provides evidence that AJ-5 is potentially an effective compound in the treatment of breast cancer.
- Full Text:
- Date Issued: 2015
Isolation, characterization and antiproliferative activity of new metabolites from the South African endemic red algal species Laurencia alfredensis
- Dziwornu, Godwin A, Caira, Mino R, de la Mare, Jo-Anne, Edkins, Adrienne L, Bolton, John J, Beukes, Denzil R, Sunassee, Suthananda N
- Authors: Dziwornu, Godwin A , Caira, Mino R , de la Mare, Jo-Anne , Edkins, Adrienne L , Bolton, John J , Beukes, Denzil R , Sunassee, Suthananda N
- Date: 2017
- Language: English
- Type: article , text
- Identifier: http://hdl.handle.net/10962/59963 , vital:27715 , https://doi:10.3390/molecules22040513
- Description: The marine red algae of the genus Laurencia have been widely studied for their structurally diverse and biologically active secondary metabolites. We report here the natural product investigation of the organic extract of a newly identified South African endemic species, Laurencia alfredensis. A sequence of column chromatography, preparative TLC and normal phase HPLC resulted in the isolation of eleven compounds comprising three labdane-type diterpenes (1-3), four polyether triterpenes (4-7), three cholestane-type ecdysteroids (8-10) and a glycolipid (11). Compounds 1-3, 5-8 and 10 have not previously been reported, while compound 9 is reported here for the first time from a natural source and the known compound 11 isolated for the first time from the genus Laurencia. The structural elucidation and the relative configuration assignments of the compounds were accomplished by extensive use of ID- and 2D-NMR, HR-ESI-MS, UV and IR spectroscopic techniques, while the absolute configuration of compound 1 was determined by single-crystal X-ray diffraction analysis. All compounds were evaluated against the MDA-MB-231 breast and HeLa cervical cancer cell lines. Compound 2 exhibited low micromolar antiproliferative activity (IC50 = 9.3 gM) against the triple negative breast carcinoma and compound 7 was similarly active (IC50 = 8.8 gM) against the cervical cancer cell line.
- Full Text:
- Date Issued: 2017
- Authors: Dziwornu, Godwin A , Caira, Mino R , de la Mare, Jo-Anne , Edkins, Adrienne L , Bolton, John J , Beukes, Denzil R , Sunassee, Suthananda N
- Date: 2017
- Language: English
- Type: article , text
- Identifier: http://hdl.handle.net/10962/59963 , vital:27715 , https://doi:10.3390/molecules22040513
- Description: The marine red algae of the genus Laurencia have been widely studied for their structurally diverse and biologically active secondary metabolites. We report here the natural product investigation of the organic extract of a newly identified South African endemic species, Laurencia alfredensis. A sequence of column chromatography, preparative TLC and normal phase HPLC resulted in the isolation of eleven compounds comprising three labdane-type diterpenes (1-3), four polyether triterpenes (4-7), three cholestane-type ecdysteroids (8-10) and a glycolipid (11). Compounds 1-3, 5-8 and 10 have not previously been reported, while compound 9 is reported here for the first time from a natural source and the known compound 11 isolated for the first time from the genus Laurencia. The structural elucidation and the relative configuration assignments of the compounds were accomplished by extensive use of ID- and 2D-NMR, HR-ESI-MS, UV and IR spectroscopic techniques, while the absolute configuration of compound 1 was determined by single-crystal X-ray diffraction analysis. All compounds were evaluated against the MDA-MB-231 breast and HeLa cervical cancer cell lines. Compound 2 exhibited low micromolar antiproliferative activity (IC50 = 9.3 gM) against the triple negative breast carcinoma and compound 7 was similarly active (IC50 = 8.8 gM) against the cervical cancer cell line.
- Full Text:
- Date Issued: 2017
Real-time monitoring of 3T3-L1 preadipocyte differentiation using a commercially available electric cell-substrate impedance sensor system:
- Kramer, Adam H, Joos-Vandewalle, Julia, Edkins, Adrienne L, Frost, Carminita L, Prinsloo, Earl
- Authors: Kramer, Adam H , Joos-Vandewalle, Julia , Edkins, Adrienne L , Frost, Carminita L , Prinsloo, Earl
- Date: 2014
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164830 , vital:41176 , DOI: 10.1016/j.bbrc.2013.12.123
- Description: Real-time analysis offers multiple benefits over traditional end point assays. Here, we present a method of monitoring the optimisation of the growth and differentiation of murine 3T3-L1 preadipocytes to adipocytes using the commercially available ACEA xCELLigence Real-Time Cell Analyser Single Plate (RTCA SP) system. Our findings indicate that the ACEA xCELLigence RTCA SP can reproducibly monitor the primary morphological changes in pre- and post-confluent 3T3-L1 fibroblasts induced to differentiate using insulin, dexamethasone, 3-isobutyl-1-methylxanthine and rosiglitazone; and may be a viable primary method of screening compounds for adipogenic factors.
- Full Text:
- Date Issued: 2014
- Authors: Kramer, Adam H , Joos-Vandewalle, Julia , Edkins, Adrienne L , Frost, Carminita L , Prinsloo, Earl
- Date: 2014
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164830 , vital:41176 , DOI: 10.1016/j.bbrc.2013.12.123
- Description: Real-time analysis offers multiple benefits over traditional end point assays. Here, we present a method of monitoring the optimisation of the growth and differentiation of murine 3T3-L1 preadipocytes to adipocytes using the commercially available ACEA xCELLigence Real-Time Cell Analyser Single Plate (RTCA SP) system. Our findings indicate that the ACEA xCELLigence RTCA SP can reproducibly monitor the primary morphological changes in pre- and post-confluent 3T3-L1 fibroblasts induced to differentiate using insulin, dexamethasone, 3-isobutyl-1-methylxanthine and rosiglitazone; and may be a viable primary method of screening compounds for adipogenic factors.
- Full Text:
- Date Issued: 2014
Differential regulation of monocyte cytokine release by αV and β2 integrins that bind CD23:
- Edkins, Adrienne L, Borland, Gillian, Acharya, Mridu, Cogdell, Richard, Ozanne, Bradford W, Cushley, William
- Authors: Edkins, Adrienne L , Borland, Gillian , Acharya, Mridu , Cogdell, Richard , Ozanne, Bradford W , Cushley, William
- Date: 2012
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165153 , vital:41213 , DOI: 10.1111/j.1365-2567.2012.03576.x
- Description: The human soluble CD23 (sCD23) protein displays highly pleiotropic cytokine‐like activity. Monocytic cells express the sCD23‐binding integrins αVβ3, αVβ5, αMβ2 and αXβ2, but it is unclear which of these four integrins most acutely regulates sCD23‐driven cytokine release. The hypothesis that ligation of different sCD23‐binding integrins promoted release of distinct subsets of cytokines was tested. Lipopolysaccharide (LPS) and sCD23 promoted release of distinct groups of cytokines from the THP‐1 model cell line.
- Full Text:
- Date Issued: 2012
- Authors: Edkins, Adrienne L , Borland, Gillian , Acharya, Mridu , Cogdell, Richard , Ozanne, Bradford W , Cushley, William
- Date: 2012
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165153 , vital:41213 , DOI: 10.1111/j.1365-2567.2012.03576.x
- Description: The human soluble CD23 (sCD23) protein displays highly pleiotropic cytokine‐like activity. Monocytic cells express the sCD23‐binding integrins αVβ3, αVβ5, αMβ2 and αXβ2, but it is unclear which of these four integrins most acutely regulates sCD23‐driven cytokine release. The hypothesis that ligation of different sCD23‐binding integrins promoted release of distinct subsets of cytokines was tested. Lipopolysaccharide (LPS) and sCD23 promoted release of distinct groups of cytokines from the THP‐1 model cell line.
- Full Text:
- Date Issued: 2012
HSP90 interacts with the fibronectin N-terminal domains and increases matrix formation:
- Chakraborty, Abir, Boel, Natasha M-E, Edkins, Adrienne L
- Authors: Chakraborty, Abir , Boel, Natasha M-E , Edkins, Adrienne L
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165407 , vital:41241 , https://doi.org/10.3390/cells9020272
- Description: Heat shock protein 90 (HSP90) is an evolutionarily conserved chaperone protein that controls the function and stability of a wide range of cellular client proteins. Fibronectin (FN) is an extracellular client protein of HSP90, and exogenous HSP90 or inhibitors of HSP90 alter the morphology of the extracellular matrix. Here, we further characterized the HSP90 and FN interaction. FN bound to the M domain of HSP90 and interacted with both the open and closed HSP90 conformations; and the interaction was reduced in the presence of sodium molybdate. HSP90 interacted with the N-terminal regions of FN, which are known to be important for matrix assembly.
- Full Text:
- Date Issued: 2020
- Authors: Chakraborty, Abir , Boel, Natasha M-E , Edkins, Adrienne L
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165407 , vital:41241 , https://doi.org/10.3390/cells9020272
- Description: Heat shock protein 90 (HSP90) is an evolutionarily conserved chaperone protein that controls the function and stability of a wide range of cellular client proteins. Fibronectin (FN) is an extracellular client protein of HSP90, and exogenous HSP90 or inhibitors of HSP90 alter the morphology of the extracellular matrix. Here, we further characterized the HSP90 and FN interaction. FN bound to the M domain of HSP90 and interacted with both the open and closed HSP90 conformations; and the interaction was reduced in the presence of sodium molybdate. HSP90 interacted with the N-terminal regions of FN, which are known to be important for matrix assembly.
- Full Text:
- Date Issued: 2020
Hsp90α/β associates with the GSK3β/axin1/phospho-β-catenin complex in the human MCF-7 epithelial breast cancer model:
- Cooper, Leanne C, Prinsloo, Earl, Edkins, Adrienne L, Blatch, Gregory L
- Authors: Cooper, Leanne C , Prinsloo, Earl , Edkins, Adrienne L , Blatch, Gregory L
- Date: 2011
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165096 , vital:41208 , DOI: 10.1016/j.bbrc.2011.08.136
- Description: Hsp90α/β, the signal transduction chaperone, maintains intracellular communication in normal, stem, and cancer cells. The well characterised association of Hsp90α/β with its client kinases form the framework of multiple signalling networks. GSK3β, a known Hsp90α/β client, mediates β-catenin phosphorylation as part of a cytoplasmic destruction complex which targets phospho-β-catenin to the 26S proteasome. The canonical Wnt/β-catenin pathway promotes stem cell self-renewal as well as oncogenesis. The degree of Hsp90α/β involvement in Wnt/β-catenin signalling needs clarification. Here, we describe the association of Hsp90α/β with GSK3β, β-catenin, phospho-β-catenin and the molecular scaffold, axin1, in the human MCF-7 epithelial breast cancer cell model using selective inhibition of Hsp90α/β, confocal laser scanning microscopy and immunoprecipitation. Our findings suggest that Hsp90α/β modulates the phosphorylation of β-catenin by interaction in common complex with GSK3β/axin1/β-catenin.
- Full Text:
- Date Issued: 2011
- Authors: Cooper, Leanne C , Prinsloo, Earl , Edkins, Adrienne L , Blatch, Gregory L
- Date: 2011
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165096 , vital:41208 , DOI: 10.1016/j.bbrc.2011.08.136
- Description: Hsp90α/β, the signal transduction chaperone, maintains intracellular communication in normal, stem, and cancer cells. The well characterised association of Hsp90α/β with its client kinases form the framework of multiple signalling networks. GSK3β, a known Hsp90α/β client, mediates β-catenin phosphorylation as part of a cytoplasmic destruction complex which targets phospho-β-catenin to the 26S proteasome. The canonical Wnt/β-catenin pathway promotes stem cell self-renewal as well as oncogenesis. The degree of Hsp90α/β involvement in Wnt/β-catenin signalling needs clarification. Here, we describe the association of Hsp90α/β with GSK3β, β-catenin, phospho-β-catenin and the molecular scaffold, axin1, in the human MCF-7 epithelial breast cancer cell model using selective inhibition of Hsp90α/β, confocal laser scanning microscopy and immunoprecipitation. Our findings suggest that Hsp90α/β modulates the phosphorylation of β-catenin by interaction in common complex with GSK3β/axin1/β-catenin.
- Full Text:
- Date Issued: 2011
Repurposing a polymer precursor: Synthesis and in vitro medicinal potential of ferrocenyl 1, 3-benzoxazine derivatives
- Mbaba, Mziyanda, Dingle, Laura M K, Cash, Devon, de la Mare, Jo-Anne, Laming, Dustin, Taylor, Dale, Hoppe, Heinrich C, Edkins, Adrienne L, Khanye, Setshaba D
- Authors: Mbaba, Mziyanda , Dingle, Laura M K , Cash, Devon , de la Mare, Jo-Anne , Laming, Dustin , Taylor, Dale , Hoppe, Heinrich C , Edkins, Adrienne L , Khanye, Setshaba D
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165395 , vital:41240 , https://doi.org/10.1016/j.ejmech.2019.111924
- Description: Cancer and malaria remain relevant pathologies in modern medicinal chemistry endeavours. This is compounded by the threat of development of resistance to existing clinical drugs in use as first-line option for treatment of these diseases. To counter this threat, strategies such as drug repurposing and hybridization are constantly adapted in contemporary drug discovery for the expansion of the drug arsenal and generation of novel chemotypes with potential to avert or delay resistance. In the present study, a polymer precursor scaffold, 1,3-benzoxazine, has been repurposed by incorporation of an organometallic ferrocene unit to produce a novel class of compounds showing in vitro biological activity against breast cancer, malaria and trypanosomiasis.
- Full Text:
- Date Issued: 2020
- Authors: Mbaba, Mziyanda , Dingle, Laura M K , Cash, Devon , de la Mare, Jo-Anne , Laming, Dustin , Taylor, Dale , Hoppe, Heinrich C , Edkins, Adrienne L , Khanye, Setshaba D
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165395 , vital:41240 , https://doi.org/10.1016/j.ejmech.2019.111924
- Description: Cancer and malaria remain relevant pathologies in modern medicinal chemistry endeavours. This is compounded by the threat of development of resistance to existing clinical drugs in use as first-line option for treatment of these diseases. To counter this threat, strategies such as drug repurposing and hybridization are constantly adapted in contemporary drug discovery for the expansion of the drug arsenal and generation of novel chemotypes with potential to avert or delay resistance. In the present study, a polymer precursor scaffold, 1,3-benzoxazine, has been repurposed by incorporation of an organometallic ferrocene unit to produce a novel class of compounds showing in vitro biological activity against breast cancer, malaria and trypanosomiasis.
- Full Text:
- Date Issued: 2020
Plaxenone A and B: Cytotoxic halogenated monoterpenes from the South African red seaweed Plocamium maxillosum
- Knott, Michael G, de la Mare, Jo-Anne, Edkins, Adrienne L, Zhang, Angel, Stillman, Martin J, Bolton, John J, Antunes, Edith M, Beukes, Denzil R
- Authors: Knott, Michael G , de la Mare, Jo-Anne , Edkins, Adrienne L , Zhang, Angel , Stillman, Martin J , Bolton, John J , Antunes, Edith M , Beukes, Denzil R
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164446 , vital:41119 , https://doi.org/10.1016/j.phytol.2018.12.009
- Description: The endemic South African red seaweed Plocamium maxillosum (Poiret) Lamouroux produces two unusual isomeric dichlorinated cyclohexenone monoterpenes, plaxenone A and B (1 and 2). The structures of the isolated compounds were determined from spectroscopic data and their absolute configuration was determined by comparison of the experimental and calculated ECD spectra. Compounds 1 and 2 inhibit the growth of MDA-MB-231 breast cancer cells.
- Full Text:
- Date Issued: 2019
- Authors: Knott, Michael G , de la Mare, Jo-Anne , Edkins, Adrienne L , Zhang, Angel , Stillman, Martin J , Bolton, John J , Antunes, Edith M , Beukes, Denzil R
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164446 , vital:41119 , https://doi.org/10.1016/j.phytol.2018.12.009
- Description: The endemic South African red seaweed Plocamium maxillosum (Poiret) Lamouroux produces two unusual isomeric dichlorinated cyclohexenone monoterpenes, plaxenone A and B (1 and 2). The structures of the isolated compounds were determined from spectroscopic data and their absolute configuration was determined by comparison of the experimental and calculated ECD spectra. Compounds 1 and 2 inhibit the growth of MDA-MB-231 breast cancer cells.
- Full Text:
- Date Issued: 2019
Anticancer evaluation of ruthenium (III) complexes with N-donor ligands tethered to coumarin or uracil moieties:
- Gramni, Larusha, Vukea, Nyeleti, Chakraborty, Abir, Samson, William J, Dingle, Laura M K, Xulu, Bheki, de la Mare, Jo-Anne, Edkins, Adrienne L, Booysen, Irvin N
- Authors: Gramni, Larusha , Vukea, Nyeleti , Chakraborty, Abir , Samson, William J , Dingle, Laura M K , Xulu, Bheki , de la Mare, Jo-Anne , Edkins, Adrienne L , Booysen, Irvin N
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163477 , vital:41041 , DOI: 10.1016/j.ica.2019.04.01
- Description: In this study, the synthesis and characterization of new paramagnetic ruthenium(III) complexes: cis-[RuCl2(urdpa)] (1) {Hurdpa = 6-((bis(pyridin-2-ylmethyl)amino)methyl)uracil} and fac-[RuCl3(chrdpa)] (2) {chrdpa = 4-((bis(pyridin-2-ylmethyl)amino)methyl)-7-methoxycoumarin} are reported. These metal complexes have been comprehensively characterized by an array of physicochemical techniques and the X-ray solid-state structures of 1 and Hurdpa have been attained.
- Full Text:
- Date Issued: 2019
- Authors: Gramni, Larusha , Vukea, Nyeleti , Chakraborty, Abir , Samson, William J , Dingle, Laura M K , Xulu, Bheki , de la Mare, Jo-Anne , Edkins, Adrienne L , Booysen, Irvin N
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163477 , vital:41041 , DOI: 10.1016/j.ica.2019.04.01
- Description: In this study, the synthesis and characterization of new paramagnetic ruthenium(III) complexes: cis-[RuCl2(urdpa)] (1) {Hurdpa = 6-((bis(pyridin-2-ylmethyl)amino)methyl)uracil} and fac-[RuCl3(chrdpa)] (2) {chrdpa = 4-((bis(pyridin-2-ylmethyl)amino)methyl)-7-methoxycoumarin} are reported. These metal complexes have been comprehensively characterized by an array of physicochemical techniques and the X-ray solid-state structures of 1 and Hurdpa have been attained.
- Full Text:
- Date Issued: 2019
Extracellular Hsp90 and TGFP regulate adhesion, migration and anchorage independent growth in a paired colon cancer cell line model
- de la Mare, Jo-Anne, Jurgens, Tamarin, Edkins, Adrienne L
- Authors: de la Mare, Jo-Anne , Jurgens, Tamarin , Edkins, Adrienne L
- Date: 2017
- Language: English
- Type: article , text
- Identifier: http://hdl.handle.net/10962/59920 , vital:27710 , https://doi.org/10.1186/s12885-017-3190-z
- Description: Tumour metastasis remains the major cause of death in cancer patients and, to date, the mechanism and signalling pathways governing this process are not completely understood. The TGF-ß pathway is the most commonly mutated pathway in cancer, however its role in cancer progression is controversial as it can function as both a promoter and a suppressor of metastasis. Although previous studies have suggested a role for the molecular chaperone Hsp90 in regulating the TGF-ß pathway, the level at which this occurs as well as the consequences in terms of colon cancer metastasis are unknown.
- Full Text:
- Date Issued: 2017
- Authors: de la Mare, Jo-Anne , Jurgens, Tamarin , Edkins, Adrienne L
- Date: 2017
- Language: English
- Type: article , text
- Identifier: http://hdl.handle.net/10962/59920 , vital:27710 , https://doi.org/10.1186/s12885-017-3190-z
- Description: Tumour metastasis remains the major cause of death in cancer patients and, to date, the mechanism and signalling pathways governing this process are not completely understood. The TGF-ß pathway is the most commonly mutated pathway in cancer, however its role in cancer progression is controversial as it can function as both a promoter and a suppressor of metastasis. Although previous studies have suggested a role for the molecular chaperone Hsp90 in regulating the TGF-ß pathway, the level at which this occurs as well as the consequences in terms of colon cancer metastasis are unknown.
- Full Text:
- Date Issued: 2017
Synthetic, characterization and cytotoxic studies of ruthenium complexes with Schiff bases encompassing biologically relevant moieties:
- Maikoo, Sanam, Dingle, Laura M K, Chakraborty, Abir, Xulu, Bheki, Edkins, Adrienne L, Booysen, Irvin N
- Authors: Maikoo, Sanam , Dingle, Laura M K , Chakraborty, Abir , Xulu, Bheki , Edkins, Adrienne L , Booysen, Irvin N
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165429 , vital:41243 , https://doi.org/10.1016/j.poly.2020.114569
- Description: This research study describes the formation and characterization of novel paramagnetic ruthenium complexes, cis-Cl, trans-P-[RuIIICl2(carboim)(PPh3)2] with bidentate chelating carbohydrazide Schiff bases (carboim = bpc for 1, ttc for 2 and tpc for 3). These metal complexes were synthesized by the equimolar coordination reactions of trans-[RuCl2(PPh3)2] with N-[1,3-benzothiazole-2-ylmethylidene]pyridine-2-carbohydrazide (Hbpc), N-((uracil-5-yl)methylene)thiophene-2-carbohydrazide (Httc) and N-[(uracil-5-yl)methylidene]pyridine-2-carbohydrazide (Htpc), respectively. Physicochemical techniques including nuclear magnetic resonance-, electron-spin resonance- and infrared spectroscopy, UV–Vis spectrophotometry, voltammetry as well as molar conductivity measurements provided definitive determinations of the respective ruthenium compounds’ structures.
- Full Text:
- Date Issued: 2020
- Authors: Maikoo, Sanam , Dingle, Laura M K , Chakraborty, Abir , Xulu, Bheki , Edkins, Adrienne L , Booysen, Irvin N
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165429 , vital:41243 , https://doi.org/10.1016/j.poly.2020.114569
- Description: This research study describes the formation and characterization of novel paramagnetic ruthenium complexes, cis-Cl, trans-P-[RuIIICl2(carboim)(PPh3)2] with bidentate chelating carbohydrazide Schiff bases (carboim = bpc for 1, ttc for 2 and tpc for 3). These metal complexes were synthesized by the equimolar coordination reactions of trans-[RuCl2(PPh3)2] with N-[1,3-benzothiazole-2-ylmethylidene]pyridine-2-carbohydrazide (Hbpc), N-((uracil-5-yl)methylene)thiophene-2-carbohydrazide (Httc) and N-[(uracil-5-yl)methylidene]pyridine-2-carbohydrazide (Htpc), respectively. Physicochemical techniques including nuclear magnetic resonance-, electron-spin resonance- and infrared spectroscopy, UV–Vis spectrophotometry, voltammetry as well as molar conductivity measurements provided definitive determinations of the respective ruthenium compounds’ structures.
- Full Text:
- Date Issued: 2020
Knockdown of Hop downregulates RhoC expression, and decreases pseudopodia formation and migration in cancer cell lines:
- Willmer, Tarryn, Contu, Lara, Blatch, Gregory L, Edkins, Adrienne L
- Authors: Willmer, Tarryn , Contu, Lara , Blatch, Gregory L , Edkins, Adrienne L
- Date: 2013
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165196 , vital:41217 , DOI: 10.1016/j.canlet.2012.09.021
- Description: The Hsp90/Hsp70 organising protein (Hop) is a co-chaperone that mediates the interaction of Hsp90 and Hsp70 molecular chaperones during assembly of Hsp90 complexes in cells. Formation of Hsp90 complexes is a key intermediate step in the maturation and homeostasis of oncoproteins and several hormone receptors. In this paper, we demonstrate that knockdown of Hop decreased migration of Hs578T and MDA-MB-231 breast cancer cells. Hop was identified in isolated pseudopodia fractions; it colocalised with actin in lamellipodia, and co-sedimented with purified actin in vitro. Knockdown of Hop caused a decrease in the level of RhoC GTPase, and significantly inhibited pseudopodia formation in Hs578T cells. Our data suggest that Hop regulates directional cell migration by multiple unknown mechanisms.
- Full Text:
- Date Issued: 2013
- Authors: Willmer, Tarryn , Contu, Lara , Blatch, Gregory L , Edkins, Adrienne L
- Date: 2013
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165196 , vital:41217 , DOI: 10.1016/j.canlet.2012.09.021
- Description: The Hsp90/Hsp70 organising protein (Hop) is a co-chaperone that mediates the interaction of Hsp90 and Hsp70 molecular chaperones during assembly of Hsp90 complexes in cells. Formation of Hsp90 complexes is a key intermediate step in the maturation and homeostasis of oncoproteins and several hormone receptors. In this paper, we demonstrate that knockdown of Hop decreased migration of Hs578T and MDA-MB-231 breast cancer cells. Hop was identified in isolated pseudopodia fractions; it colocalised with actin in lamellipodia, and co-sedimented with purified actin in vitro. Knockdown of Hop caused a decrease in the level of RhoC GTPase, and significantly inhibited pseudopodia formation in Hs578T cells. Our data suggest that Hop regulates directional cell migration by multiple unknown mechanisms.
- Full Text:
- Date Issued: 2013
NMR structural elucidation of channaine, an unusual alkaloid from Sceletium tortuosum:
- Veale, Clinton G L, Chen, Weiyang, Chaudhary, Sushil, Kituyi, Sarah N, Isaacs, Michelle, Hoppe, Heinrich C, Edkins, Adrienne L, Combrinck, Sandra, Mehari, Bewketu, Viljoen, Alvaro
- Authors: Veale, Clinton G L , Chen, Weiyang , Chaudhary, Sushil , Kituyi, Sarah N , Isaacs, Michelle , Hoppe, Heinrich C , Edkins, Adrienne L , Combrinck, Sandra , Mehari, Bewketu , Viljoen, Alvaro
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164345 , vital:41110 , DOI: 10.1016/j.phytol.2017.11.018
- Description: Chemical interrogation of the Sceletium genus and Amaryllidaceae family of plants has yielded a diverse array of aryl-hydroindole containing alkaloids. Included in this class is channaine, which was tentatively identified, without comprehensive structural elucidation from Sceletium tortuosum in 1957. Following its isolation from S. strictum, the structure of channaine was eventually resolved by X-ray crystallographic analysis, which revealed an unusual cage-like ring structure at the interface of two aryl-hydroindole subunits. However, since this report in 1978, channaine has not re-appeared in the literature. In this letter, the full NMR characterisation of channaine, isolated from S. tortuosum collected from St Helena in the Western Cape Province of South Africa, is reported for the first time.
- Full Text:
- Date Issued: 2018
- Authors: Veale, Clinton G L , Chen, Weiyang , Chaudhary, Sushil , Kituyi, Sarah N , Isaacs, Michelle , Hoppe, Heinrich C , Edkins, Adrienne L , Combrinck, Sandra , Mehari, Bewketu , Viljoen, Alvaro
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164345 , vital:41110 , DOI: 10.1016/j.phytol.2017.11.018
- Description: Chemical interrogation of the Sceletium genus and Amaryllidaceae family of plants has yielded a diverse array of aryl-hydroindole containing alkaloids. Included in this class is channaine, which was tentatively identified, without comprehensive structural elucidation from Sceletium tortuosum in 1957. Following its isolation from S. strictum, the structure of channaine was eventually resolved by X-ray crystallographic analysis, which revealed an unusual cage-like ring structure at the interface of two aryl-hydroindole subunits. However, since this report in 1978, channaine has not re-appeared in the literature. In this letter, the full NMR characterisation of channaine, isolated from S. tortuosum collected from St Helena in the Western Cape Province of South Africa, is reported for the first time.
- Full Text:
- Date Issued: 2018
Heterodimer formation by Oct4 and Smad3 differentially regulates epithelial-to-mesenchymal transition-associated factors in breast cancer progression:
- Mandal, Gunjan, Biswas, Subir, Chowdhury, Sougata R, Chatterjee, Annesha, Purohit, Suman, Khamaru, Poulomi, Chakraborty, Sayan, Mandal, Palash K, Gupta, Arnab, de la Mare, Jo-Anne, Edkins, Adrienne L, Bhattacharyya, Arindam
- Authors: Mandal, Gunjan , Biswas, Subir , Chowdhury, Sougata R , Chatterjee, Annesha , Purohit, Suman , Khamaru, Poulomi , Chakraborty, Sayan , Mandal, Palash K , Gupta, Arnab , de la Mare, Jo-Anne , Edkins, Adrienne L , Bhattacharyya, Arindam
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164907 , vital:41183 , DOI: 10.1016/j.bbadis.2018.03.010
- Description: The multifunctional cytokine TGF-β crucially participates in breast cancer (BCa) metastasis and works differently in the disease stages, thus contributing in BCa progression. We address connections between TGF-β and the stem cell-related transcription factor (TF) Oct4 in BCa. In 147 BCa patients with infiltrating duct carcinoma, we identified a significantly higher number of cases with both moderate/high Oct4 expression and high TGF-β in late stages compared to early stages of the disease.
- Full Text:
- Date Issued: 2018
- Authors: Mandal, Gunjan , Biswas, Subir , Chowdhury, Sougata R , Chatterjee, Annesha , Purohit, Suman , Khamaru, Poulomi , Chakraborty, Sayan , Mandal, Palash K , Gupta, Arnab , de la Mare, Jo-Anne , Edkins, Adrienne L , Bhattacharyya, Arindam
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164907 , vital:41183 , DOI: 10.1016/j.bbadis.2018.03.010
- Description: The multifunctional cytokine TGF-β crucially participates in breast cancer (BCa) metastasis and works differently in the disease stages, thus contributing in BCa progression. We address connections between TGF-β and the stem cell-related transcription factor (TF) Oct4 in BCa. In 147 BCa patients with infiltrating duct carcinoma, we identified a significantly higher number of cases with both moderate/high Oct4 expression and high TGF-β in late stages compared to early stages of the disease.
- Full Text:
- Date Issued: 2018
The in vitro antiplasmodial and antiproliferative activity of new ferrocene-based α-aminocresols targeting hemozoin inhibition and DNA interaction:
- Mbaba, Mziyanda, Dingle, Laura M K, Swart, Tarryn, Cash, Devon, Laming, Dustin, de la Mare, Jo-Anne, Taylor, Dale, Hoppe, Heinrich C, Biot, Christophe, Edkins, Adrienne L, Khanye, Setshaba D
- Authors: Mbaba, Mziyanda , Dingle, Laura M K , Swart, Tarryn , Cash, Devon , Laming, Dustin , de la Mare, Jo-Anne , Taylor, Dale , Hoppe, Heinrich C , Biot, Christophe , Edkins, Adrienne L , Khanye, Setshaba D
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/149347 , vital:38827 , https://0-doi.org.wam.seals.ac.za/10.1002/cbic.202000132
- Description: Compounds incorporating ferrocene in a aminocresol scaffold showed antiplasmodial and anticancer activity. SAR studies revealed that an OH group and rotatable C–NH bond are vital for biological activity, with spectrophotometric techniques and docking simulations suggesting a dual mode of action involving hemozoin inhibition and DNA interaction. Targeting multiple pathways could delay the development of clinical resistance.
- Full Text:
- Date Issued: 2020
- Authors: Mbaba, Mziyanda , Dingle, Laura M K , Swart, Tarryn , Cash, Devon , Laming, Dustin , de la Mare, Jo-Anne , Taylor, Dale , Hoppe, Heinrich C , Biot, Christophe , Edkins, Adrienne L , Khanye, Setshaba D
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/149347 , vital:38827 , https://0-doi.org.wam.seals.ac.za/10.1002/cbic.202000132
- Description: Compounds incorporating ferrocene in a aminocresol scaffold showed antiplasmodial and anticancer activity. SAR studies revealed that an OH group and rotatable C–NH bond are vital for biological activity, with spectrophotometric techniques and docking simulations suggesting a dual mode of action involving hemozoin inhibition and DNA interaction. Targeting multiple pathways could delay the development of clinical resistance.
- Full Text:
- Date Issued: 2020
The African coelacanth genome provides insights into tetrapod evolution:
- Amemiya, Chris T, Alföldi, Jessica, Lee, Alison P, Fan, Shaohua, Philippe, Herve´, MacCallum, Iain, Braasch, Ingo, Manousaki, Tereza, Schneider, Igor, Rohner, Nicolas, Organ, Chris, Chalopin, Domitille, Smith, Jeramiah J, Robinson, Mark, Dorrington, Rosemary A, Gerdol, Marco, Aken, Bronwen, Biscotti, Maria Assunta, Barucca, Marco, Baurain, Denis, Berlin, Aaron, Blatch, Gregory L, Buonocore, Francesco, Burmester, Thorsten, Campbell, Michael S, Canapa, Adriana, Cannon, John P, Christoffels, Alan, De Moro, Gianluca, Edkins, Adrienne L, Fan, Lin, Fausto, Anna Maria, Feiner, Nathalie, Forconi, Mariko, Gamieldien, Junaid, Gnerre, Sante, Gnirke, Andreas, Goldstone, Jared V, Haerty, Wilfried, Hahn, Mark E, Hesse, Uljana, Hoffmann, Steve, Johnson, Jeremy, Karchner, Sibel I, Kuraku, Shigehiro, Lara, Marcia, Levin, Joshua Z, Litman, Gary W, Mauceli, Evan, Miyake, Tsutomu, Mueller, M Gail, Nelson, David R, Nitsche, Anne, Olmo, Ettore, Ota, Tatsuya, Pallavicini, Alberto, Panji, Sumir, Picone, Barbara, Ponting, Chris P, Prohaska, Sonja J, Przybylski, Dariusz, Ratan Saha, Nil, Ravi, Vydianathan, Ribeiro, Filipe J, Sauka-Spengler, Tatjana, Scapigliati, Giuseppe, Searle, Stephen M J, Sharpe, Ted, Simakov, Oleg, Stadler, Peter F, Stegeman, John J, Sumiyama, Kenta, Tabbaa, Diana, Tafer, Hakim, Turner-Maier, Jason, van Heusden, Peter, White, Simon, Williams, Louise, Yandell, Mark, Brinkmann, Henner, Volff, Jean-Nicolas, Tabin, Clifford J, Shubin, Neil, Schartl, Manfred, Jaffe, David B, Postlethwait, John H, Venkatesh, Byrappa, Di Palma, Frederica, Lander, Eric S, Meyer, Axel, Lindblad-Toh, Kerstin
- Authors: Amemiya, Chris T , Alföldi, Jessica , Lee, Alison P , Fan, Shaohua , Philippe, Herve´ , MacCallum, Iain , Braasch, Ingo , Manousaki, Tereza , Schneider, Igor , Rohner, Nicolas , Organ, Chris , Chalopin, Domitille , Smith, Jeramiah J , Robinson, Mark , Dorrington, Rosemary A , Gerdol, Marco , Aken, Bronwen , Biscotti, Maria Assunta , Barucca, Marco , Baurain, Denis , Berlin, Aaron , Blatch, Gregory L , Buonocore, Francesco , Burmester, Thorsten , Campbell, Michael S , Canapa, Adriana , Cannon, John P , Christoffels, Alan , De Moro, Gianluca , Edkins, Adrienne L , Fan, Lin , Fausto, Anna Maria , Feiner, Nathalie , Forconi, Mariko , Gamieldien, Junaid , Gnerre, Sante , Gnirke, Andreas , Goldstone, Jared V , Haerty, Wilfried , Hahn, Mark E , Hesse, Uljana , Hoffmann, Steve , Johnson, Jeremy , Karchner, Sibel I , Kuraku, Shigehiro , Lara, Marcia , Levin, Joshua Z , Litman, Gary W , Mauceli, Evan , Miyake, Tsutomu , Mueller, M Gail , Nelson, David R , Nitsche, Anne , Olmo, Ettore , Ota, Tatsuya , Pallavicini, Alberto , Panji, Sumir , Picone, Barbara , Ponting, Chris P , Prohaska, Sonja J , Przybylski, Dariusz , Ratan Saha, Nil , Ravi, Vydianathan , Ribeiro, Filipe J , Sauka-Spengler, Tatjana , Scapigliati, Giuseppe , Searle, Stephen M J , Sharpe, Ted , Simakov, Oleg , Stadler, Peter F , Stegeman, John J , Sumiyama, Kenta , Tabbaa, Diana , Tafer, Hakim , Turner-Maier, Jason , van Heusden, Peter , White, Simon , Williams, Louise , Yandell, Mark , Brinkmann, Henner , Volff, Jean-Nicolas , Tabin, Clifford J , Shubin, Neil , Schartl, Manfred , Jaffe, David B , Postlethwait, John H , Venkatesh, Byrappa , Di Palma, Frederica , Lander, Eric S , Meyer, Axel , Lindblad-Toh, Kerstin
- Date: 2013
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165030 , vital:41202 , DOI: 10.1038/nature12027
- Description: The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
- Full Text:
- Date Issued: 2013
- Authors: Amemiya, Chris T , Alföldi, Jessica , Lee, Alison P , Fan, Shaohua , Philippe, Herve´ , MacCallum, Iain , Braasch, Ingo , Manousaki, Tereza , Schneider, Igor , Rohner, Nicolas , Organ, Chris , Chalopin, Domitille , Smith, Jeramiah J , Robinson, Mark , Dorrington, Rosemary A , Gerdol, Marco , Aken, Bronwen , Biscotti, Maria Assunta , Barucca, Marco , Baurain, Denis , Berlin, Aaron , Blatch, Gregory L , Buonocore, Francesco , Burmester, Thorsten , Campbell, Michael S , Canapa, Adriana , Cannon, John P , Christoffels, Alan , De Moro, Gianluca , Edkins, Adrienne L , Fan, Lin , Fausto, Anna Maria , Feiner, Nathalie , Forconi, Mariko , Gamieldien, Junaid , Gnerre, Sante , Gnirke, Andreas , Goldstone, Jared V , Haerty, Wilfried , Hahn, Mark E , Hesse, Uljana , Hoffmann, Steve , Johnson, Jeremy , Karchner, Sibel I , Kuraku, Shigehiro , Lara, Marcia , Levin, Joshua Z , Litman, Gary W , Mauceli, Evan , Miyake, Tsutomu , Mueller, M Gail , Nelson, David R , Nitsche, Anne , Olmo, Ettore , Ota, Tatsuya , Pallavicini, Alberto , Panji, Sumir , Picone, Barbara , Ponting, Chris P , Prohaska, Sonja J , Przybylski, Dariusz , Ratan Saha, Nil , Ravi, Vydianathan , Ribeiro, Filipe J , Sauka-Spengler, Tatjana , Scapigliati, Giuseppe , Searle, Stephen M J , Sharpe, Ted , Simakov, Oleg , Stadler, Peter F , Stegeman, John J , Sumiyama, Kenta , Tabbaa, Diana , Tafer, Hakim , Turner-Maier, Jason , van Heusden, Peter , White, Simon , Williams, Louise , Yandell, Mark , Brinkmann, Henner , Volff, Jean-Nicolas , Tabin, Clifford J , Shubin, Neil , Schartl, Manfred , Jaffe, David B , Postlethwait, John H , Venkatesh, Byrappa , Di Palma, Frederica , Lander, Eric S , Meyer, Axel , Lindblad-Toh, Kerstin
- Date: 2013
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165030 , vital:41202 , DOI: 10.1038/nature12027
- Description: The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
- Full Text:
- Date Issued: 2013