Human FN1 is regulated by the heat-shock response
- Authors: Dhanani, Karim Colin Hassan
- Date: 2015
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/193487 , vital:45336
- Description: Heat shock protein 90 (Hsp90) and heat shock factors (HSFs) are known to be involved in the epigenetic regulation of several fundamental oncogenic genes. Fibronectin (FN) is an extracellular matrix (ECM) glycoprotein which plays key roles in cell adhesion and migration. Hsp90 binds directly to FN and Hsp90 inhibition has been shown to regulate FN protein levels and matrix formation. Where inhibition of Hsp90 with a C-terminal inhibitor (novobiocin) induced the loss of FN matrix, treatment with an N-terminal inhibitor (geldanamycin) increased FN matrix levels. GA treatment induced a strong dose and time dependent increase in FN1 promoter activity and increased total FN mRNA respectively. By contrast, NOV showed no increase in the promoter activity and no change in the expression of FN mRNA. As GA is known to induce the stress response, we investigated the relationship between the cell stress machinery and the transcriptional regulation of FN. Three putative heat shock elements (HSEs) were identified in the FN1 promoter. The loss of two of the three identified putative HSEs resulted in a loss in the basal transcriptional activity of the FN1 promoter in our reporter model. This was in addition to the loss of the induction of transcriptional activity with GA treatment observed with the full-length promoter. Binding of HSF1 to one of the putative HSEs, which was identified as potentially functional from the truncation analysis, was confirmed using ChIP. The occupancy of this HSE by HSF1 was shown to increase with GA treatment. These data support the hypothesis that FN1 is a functional HSF1 target gene. The 5' promoter regions of seven additional ECM protein encoding genes were analysed and mRNA levels were detected by quantitative RT-PCR upon treatment with GA. Collagen 4 _2 and laminin _3 mRNA were found to increase in the presence of GA, whereas collagen 4 _3 and osteopontin showed no change. Similarly to FN1, these data indicate that a subset of ECM genes may be under the regulation of the HSF1 mediated heat-shock response. This may have implications for our understanding of ECM dynamics in cancer, where the clinical application of Hsp90 inhibitors is intended. Additionally, our data provide a poten- tial underpinning for the role of the HSF1 mediated heat-shock response in several fibrotic and metabolic stress related pathologies. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2015
- Full Text:
- Date Issued: 2015
- Authors: Dhanani, Karim Colin Hassan
- Date: 2015
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/193487 , vital:45336
- Description: Heat shock protein 90 (Hsp90) and heat shock factors (HSFs) are known to be involved in the epigenetic regulation of several fundamental oncogenic genes. Fibronectin (FN) is an extracellular matrix (ECM) glycoprotein which plays key roles in cell adhesion and migration. Hsp90 binds directly to FN and Hsp90 inhibition has been shown to regulate FN protein levels and matrix formation. Where inhibition of Hsp90 with a C-terminal inhibitor (novobiocin) induced the loss of FN matrix, treatment with an N-terminal inhibitor (geldanamycin) increased FN matrix levels. GA treatment induced a strong dose and time dependent increase in FN1 promoter activity and increased total FN mRNA respectively. By contrast, NOV showed no increase in the promoter activity and no change in the expression of FN mRNA. As GA is known to induce the stress response, we investigated the relationship between the cell stress machinery and the transcriptional regulation of FN. Three putative heat shock elements (HSEs) were identified in the FN1 promoter. The loss of two of the three identified putative HSEs resulted in a loss in the basal transcriptional activity of the FN1 promoter in our reporter model. This was in addition to the loss of the induction of transcriptional activity with GA treatment observed with the full-length promoter. Binding of HSF1 to one of the putative HSEs, which was identified as potentially functional from the truncation analysis, was confirmed using ChIP. The occupancy of this HSE by HSF1 was shown to increase with GA treatment. These data support the hypothesis that FN1 is a functional HSF1 target gene. The 5' promoter regions of seven additional ECM protein encoding genes were analysed and mRNA levels were detected by quantitative RT-PCR upon treatment with GA. Collagen 4 _2 and laminin _3 mRNA were found to increase in the presence of GA, whereas collagen 4 _3 and osteopontin showed no change. Similarly to FN1, these data indicate that a subset of ECM genes may be under the regulation of the HSF1 mediated heat-shock response. This may have implications for our understanding of ECM dynamics in cancer, where the clinical application of Hsp90 inhibitors is intended. Additionally, our data provide a poten- tial underpinning for the role of the HSF1 mediated heat-shock response in several fibrotic and metabolic stress related pathologies. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2015
- Full Text:
- Date Issued: 2015
In silico analysis of plasmodium falciparum Hsp70-x for potential binding sites and hits
- Authors: Amusengeri, Arnold
- Date: 2017
- Subjects: Uncatalogued
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/59136 , vital:27435
- Description: Restricted access-thesis embargoed for 1 year - release date April 2019
- Full Text:
- Date Issued: 2017
- Authors: Amusengeri, Arnold
- Date: 2017
- Subjects: Uncatalogued
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/59136 , vital:27435
- Description: Restricted access-thesis embargoed for 1 year - release date April 2019
- Full Text:
- Date Issued: 2017
An evaluation of the cytotoxic activities of novel artemisinin derivatives: towards targeted therapies for triple-negative breast cancers (TNBC)
- Authors: Kajewole, Deborah Ifeoluwa
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/163329 , vital:41029 , doi:10.21504/10962/163329
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020.
- Full Text:
- Date Issued: 2020
- Authors: Kajewole, Deborah Ifeoluwa
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/163329 , vital:41029 , doi:10.21504/10962/163329
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020.
- Full Text:
- Date Issued: 2020
Analysis of the regulation of HSP90α expression upon differentiation of C2C12 cells
- Authors: Holm, Nathan Christopher
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163318 , vital:41028
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020.
- Full Text:
- Date Issued: 2020
- Authors: Holm, Nathan Christopher
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163318 , vital:41028
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020.
- Full Text:
- Date Issued: 2020
Bioinformatic analysis of Aminoacyl tRNA Synthetases as potential antimalarial drug targets
- Authors: Nyamai, Dorothy Wavinya
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164579 , vital:41142 , doi:10.21504/10962/164579
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Nyamai, Dorothy Wavinya
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164579 , vital:41142 , doi:10.21504/10962/164579
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
Comparative analysis of the known Hop1b and the novel Hop1a isoforms of the Hop gene
- Authors: Makhubu, Portia
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164311 , vital:41108 , doi:10.21504/10962/164311
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Makhubu, Portia
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164311 , vital:41108 , doi:10.21504/10962/164311
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
Hop as an anti-cancer drug target
- Vaaltyn, Michaelone Chantelle
- Authors: Vaaltyn, Michaelone Chantelle
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164704 , vital:41156 , doi:10.21504/10962/164704
- Description: Thesis (PhD)--Rhodes University, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Vaaltyn, Michaelone Chantelle
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164704 , vital:41156 , doi:10.21504/10962/164704
- Description: Thesis (PhD)--Rhodes University, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
Investigating the relationship between Heat Shock Proteins and HIV Transactivator of Transcription
- Authors: Flax, Lili Marie
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163307 , vital:41027
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020.
- Full Text:
- Date Issued: 2020
- Authors: Flax, Lili Marie
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163307 , vital:41027
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020.
- Full Text:
- Date Issued: 2020
Multiplexed Mass Spectrometry: Single, On-Bead, Detection Analysis Using MALDI-TOF MS
- Authors: Twala, Busisiwe Victoria
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164693 , vital:41155 , doi:10.21504/10962/164693
- Description: Thesis (PhD)--Rhodes University, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Twala, Busisiwe Victoria
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164693 , vital:41155 , doi:10.21504/10962/164693
- Description: Thesis (PhD)--Rhodes University, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
Nutrient impacts on grasses and legumes growing in communal pasture soil in relation to mycorrhizal activity
- Authors: Mkile, Zolani
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164512 , vital:41125 , doi:10.21504/10962/164512
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Mkile, Zolani
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164512 , vital:41125 , doi:10.21504/10962/164512
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
Production, purification and characterization of a multifunctional, thermostable and acido/alkaline stable putative xylanase from the psychrotrophic bacterium, Sphingomonas aerolata
- Authors: Mathibe, Brian Nkanyiso
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164478 , vital:41122
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Mathibe, Brian Nkanyiso
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164478 , vital:41122
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
The novobiocin-induced turnover of fibronectin via low density lipoprotein receptor-related protein 1 alters matrix morphology with physiological consequences on cell growth and migration
- Authors: Boёl, Natasha Marie-Eraine
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/114778 , vital:34034 , 10.21504/10962/114778
- Description: Fibronectin (FN), an extracellular matrix protein, is secreted as a soluble dimer which is assembled into an insoluble extracellular matrix. The dynamics of FN matrix assembly and degradation play a large role in cell migration and invasion thereby contributing to the metastatic potential of cancer cells. Previous studies have shown the direct binding of Heat Shock Protein 90 kDa (Hsp90) and FN in vitro, and that inhibition of Hsp90 with novobiocin (NOV) caused internalisation of the FN matrix. Low density lipoprotein receptor-related protein 1 (LRP1) is a ubiquitous receptor known to bind both Hsp90 and FN. Using an LRP1 expressing Hs578T breast cancer cell line and an isogenic mouse embryonic fibroblast (MEF) model system of differential LRP1 expression we demonstrate that LRP1 is involved in turnover of FN in response to C-terminal Hsp90 inhibition. The first objective of this study was to identify the mechanism of NOV-induced LRP1-mediated FN turnover. Our data show that NOV-mediated FN turnover via LRP1 did not require the activity of matrix metalloproteinases (MMPs), which play an important role in processing and degradation of the extracellular matrix and FN. In addition, the levels of the main FN receptor responsible for its extracellular assembly, β1-integrin, did not change in response to NOV. LRP1 is known to undergo regulated intramembrane proteolysis (RIP) which generates smaller fragments that may translocate to the nucleus and modulate gene transcription. Using inhibitors of LRP1 cleavage and nuclear fractionation we determined that LRP1 processing was not required for the NOV-induced FN response suggesting that a mechanism unrelated to LRP1 RIP is involved. A possible mechanism may be in altered Hsp90-LRP1 cell signalling as we observed disruption of the FN-Hsp90-LRP1 complex at the cell surface in NOV treated cells. How this affects downstream eHsp90-LRP1 signalling is still to be determined but may be related to a significant increase in phospho-AKT and loss of phospho-ERK upon NOV-treatment; two key signalling proteins involved in FN matrix regulation and which are downstream of LRP1 signalling. The second objective of this study was to determine the physiological consequences associated with FN turnover in response to NOV treatment. Using migration assays we demonstrated that levels of insoluble matrix-associated FN and FN concentration are not solely responsible for migratory capacity of cells on decellularized extracellular matrices, but rather that structural composition and integrity of the matrix plays a bigger role. Using confocal and scanning electron microscopy, we identified NOV treated matrices to be flatter, less mature and contain thicker, rope-like FN fibrils to which cells adhered better but were generally less proliferative. Comparatively, cells adhered less to the more mature and 3-dimensional untreated matrices but exhibited increased spreading and cell growth, which may in part be due to the thinner fibrils and web-like matrix. In summary, this study substantiates the role of LRP1 in NOV-mediated FN turnover, and provides new insights into the possible mechanisms of the Hsp90-LRP1 mediated loss of FN matrix. This is the first study to demonstrate some of the functional consequences related to FN turnover by NOV at the ECM level. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text: false
- Date Issued: 2020
- Authors: Boёl, Natasha Marie-Eraine
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/114778 , vital:34034 , 10.21504/10962/114778
- Description: Fibronectin (FN), an extracellular matrix protein, is secreted as a soluble dimer which is assembled into an insoluble extracellular matrix. The dynamics of FN matrix assembly and degradation play a large role in cell migration and invasion thereby contributing to the metastatic potential of cancer cells. Previous studies have shown the direct binding of Heat Shock Protein 90 kDa (Hsp90) and FN in vitro, and that inhibition of Hsp90 with novobiocin (NOV) caused internalisation of the FN matrix. Low density lipoprotein receptor-related protein 1 (LRP1) is a ubiquitous receptor known to bind both Hsp90 and FN. Using an LRP1 expressing Hs578T breast cancer cell line and an isogenic mouse embryonic fibroblast (MEF) model system of differential LRP1 expression we demonstrate that LRP1 is involved in turnover of FN in response to C-terminal Hsp90 inhibition. The first objective of this study was to identify the mechanism of NOV-induced LRP1-mediated FN turnover. Our data show that NOV-mediated FN turnover via LRP1 did not require the activity of matrix metalloproteinases (MMPs), which play an important role in processing and degradation of the extracellular matrix and FN. In addition, the levels of the main FN receptor responsible for its extracellular assembly, β1-integrin, did not change in response to NOV. LRP1 is known to undergo regulated intramembrane proteolysis (RIP) which generates smaller fragments that may translocate to the nucleus and modulate gene transcription. Using inhibitors of LRP1 cleavage and nuclear fractionation we determined that LRP1 processing was not required for the NOV-induced FN response suggesting that a mechanism unrelated to LRP1 RIP is involved. A possible mechanism may be in altered Hsp90-LRP1 cell signalling as we observed disruption of the FN-Hsp90-LRP1 complex at the cell surface in NOV treated cells. How this affects downstream eHsp90-LRP1 signalling is still to be determined but may be related to a significant increase in phospho-AKT and loss of phospho-ERK upon NOV-treatment; two key signalling proteins involved in FN matrix regulation and which are downstream of LRP1 signalling. The second objective of this study was to determine the physiological consequences associated with FN turnover in response to NOV treatment. Using migration assays we demonstrated that levels of insoluble matrix-associated FN and FN concentration are not solely responsible for migratory capacity of cells on decellularized extracellular matrices, but rather that structural composition and integrity of the matrix plays a bigger role. Using confocal and scanning electron microscopy, we identified NOV treated matrices to be flatter, less mature and contain thicker, rope-like FN fibrils to which cells adhered better but were generally less proliferative. Comparatively, cells adhered less to the more mature and 3-dimensional untreated matrices but exhibited increased spreading and cell growth, which may in part be due to the thinner fibrils and web-like matrix. In summary, this study substantiates the role of LRP1 in NOV-mediated FN turnover, and provides new insights into the possible mechanisms of the Hsp90-LRP1 mediated loss of FN matrix. This is the first study to demonstrate some of the functional consequences related to FN turnover by NOV at the ECM level. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text: false
- Date Issued: 2020
The Role of HSP70/HSP90 Organizing Protein (Hop) in the Heat Shock Factor 1 (HSF1)-mediated Stress Response
- Authors: Chakraborty, Abantika
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/163204 , vital:41018 , doi:10.21504/10962/163204
- Description: Molecular chaperones regulate cellular proteostasis. They control protein conformation and prevent misfolding and aggregation under both normal and stressful environments, ultimately resulting in cell survival. The project aimed to understand the role of the HSP70 – HSP90 Organizing Protein (Hop/STIP1) in the survival of stressed cells and the function of the stress-responsive transcription factor, Heat Shock Factor 1 (HSF1). HSF1 protein levels were significantly reduced in Hop-depleted HEK293T cells compared to controls by ELISA, western blot, and mass spectrometry. HSF1 transcriptional activity at the HSP70 promoter, and binding of a biotinylated HSE oligonucleotide under basal conditions were significantly reduced, consistent with the reduced levels of HSF1. In response to heat shock, HSF1 levels in Hop-depleted cells increased to that of controls, but there was still significantly lowerHSF1 transcriptional activity and HSE binding. Hop-depleted HEK293T cells were more sensitive than controls to the HSF1 inhibitor KRIBB11 and showed reduced short-term and long-term proliferation. Unlike the HSP90 inhibitor 17-DMAG, which had no effect, the HSP70 inhibitor JG98, further decreased the levels of HSF1 in Hop-depleted cells, suggesting a role for HSP70 in the Hop-mediated effects. There was punctate nuclear staining for HSF1 in Hop-depleted cells under both basal and heat shock conditions, as well as reduced nuclear localization and increased cytoplasmic accumulation of HSF1 in response to heat shock. Hop and HSF1 colocalized in cells, and HSF1 could be isolated in complex with Hop and HSP70. Loss of Hop reduced HSF1 in HSP70complexes but did not affect HSF1 abundance in HSP90 complexes. Hop-depleted cells showed reduced short-term and long-term survival compared to controls, an effect that was potentiated by the JG98 HSP70 inhibitor. Taken together, these data suggest that Hop regulation of HSF1activity is via a mechanism involving reductions in HSP70 interaction, as well as reduced nuclear localization, and DNA binding, and is consistent with reduced cellular fitness under basal and stress conditions. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Chakraborty, Abantika
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/163204 , vital:41018 , doi:10.21504/10962/163204
- Description: Molecular chaperones regulate cellular proteostasis. They control protein conformation and prevent misfolding and aggregation under both normal and stressful environments, ultimately resulting in cell survival. The project aimed to understand the role of the HSP70 – HSP90 Organizing Protein (Hop/STIP1) in the survival of stressed cells and the function of the stress-responsive transcription factor, Heat Shock Factor 1 (HSF1). HSF1 protein levels were significantly reduced in Hop-depleted HEK293T cells compared to controls by ELISA, western blot, and mass spectrometry. HSF1 transcriptional activity at the HSP70 promoter, and binding of a biotinylated HSE oligonucleotide under basal conditions were significantly reduced, consistent with the reduced levels of HSF1. In response to heat shock, HSF1 levels in Hop-depleted cells increased to that of controls, but there was still significantly lowerHSF1 transcriptional activity and HSE binding. Hop-depleted HEK293T cells were more sensitive than controls to the HSF1 inhibitor KRIBB11 and showed reduced short-term and long-term proliferation. Unlike the HSP90 inhibitor 17-DMAG, which had no effect, the HSP70 inhibitor JG98, further decreased the levels of HSF1 in Hop-depleted cells, suggesting a role for HSP70 in the Hop-mediated effects. There was punctate nuclear staining for HSF1 in Hop-depleted cells under both basal and heat shock conditions, as well as reduced nuclear localization and increased cytoplasmic accumulation of HSF1 in response to heat shock. Hop and HSF1 colocalized in cells, and HSF1 could be isolated in complex with Hop and HSP70. Loss of Hop reduced HSF1 in HSP70complexes but did not affect HSF1 abundance in HSP90 complexes. Hop-depleted cells showed reduced short-term and long-term survival compared to controls, an effect that was potentiated by the JG98 HSP70 inhibitor. Taken together, these data suggest that Hop regulation of HSF1activity is via a mechanism involving reductions in HSP70 interaction, as well as reduced nuclear localization, and DNA binding, and is consistent with reduced cellular fitness under basal and stress conditions. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
The role of the Hop co-chaperone in the formation of Hsp90 complexes: chaperone link to glycolysis
- Authors: Maharaj, Shantal
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/163593 , vital:41051 , doi:10.21504/10962/163593
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Maharaj, Shantal
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/163593 , vital:41051 , doi:10.21504/10962/163593
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
Exploring targeted metagenomics and untargeted metabolomics for characterising aquaponics bacterial ecology and phytochemistry
- Authors: Abraham, Benjamin Melakail
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/192453 , vital:45227
- Description: Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Abraham, Benjamin Melakail
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/192453 , vital:45227
- Description: Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2021
- Full Text:
- Date Issued: 2021-10-29
Exploring the use of in vitro colorimetric and bioluminescence assays to distinguish between Arf GTPase isoforms and detect Arf GTPase activity
- Authors: Woolf, Alexander Robert
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/192582 , vital:45240
- Description: Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Woolf, Alexander Robert
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/192582 , vital:45240
- Description: Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2021
- Full Text:
- Date Issued: 2021-10-29
Hop-mediated alteration of cellular metabolism in KSHV infection
- Authors: Kirigin, Elisa
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/192477 , vital:45229
- Description: Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Kirigin, Elisa
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/192477 , vital:45229
- Description: Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2021
- Full Text:
- Date Issued: 2021-10-29
Effects of hydraulic fracking fluid on soil microbial composition and diversity
- Authors: Sianyuka, Nicolette
- Date: 2022-04-06
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/232366 , vital:49985
- Description: Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
- Date Issued: 2022-04-06
- Authors: Sianyuka, Nicolette
- Date: 2022-04-06
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/232366 , vital:49985
- Description: Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
- Date Issued: 2022-04-06
Computational analysis of known drug resistant mutants of Plasmodium falciparum Dihydrofolate Reductase (PfDHFR) and screening for novel antifolates against the enzyme
- Authors: Tata, Rolland Bantar
- Date: 2022-04-08
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/234184 , vital:50170
- Description: Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
- Date Issued: 2022-04-08
- Authors: Tata, Rolland Bantar
- Date: 2022-04-08
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/234184 , vital:50170
- Description: Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
- Date Issued: 2022-04-08
Diversified computational approaches for the identification of orthosteric drugs, allosteric modulators and unveiling drug resistance mechanisms: application to infectious diseases
- Authors: Boateng, Rita Afriyie
- Date: 2022-04-08
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/234173 , vital:50169
- Description: Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
- Date Issued: 2022-04-08
- Authors: Boateng, Rita Afriyie
- Date: 2022-04-08
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/234173 , vital:50169
- Description: Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
- Date Issued: 2022-04-08