- Title
- HOP expression is regulated by p53 and RAS and characteristic of a cancer gene signature
- Creator
- Mattison, Stacey A
- Creator
- Blatch, Gregory L
- Creator
- Edkins, Adrienne L
- Date Issued
- 2018
- Date
- 2018
- Type
- text
- Type
- article
- Identifier
- http://hdl.handle.net/10962/66278
- Identifier
- vital:28928
- Identifier
- https://doi.org/10.1007/s12192-016-0755-8
- Description
- publisher version
- Description
- The Hsp70/Hsp90 organising protein (HOP) is a co-chaperone essential for client protein transfer from Hsp70 to Hsp90 within the Hsp90 chaperone machine. Although HOP is upregulated in various cancers, there is limited information from in vitro studies on how HOP expression is regulated in cancer. The main objective of this study was to identify the HOP promoter and investigate its activity in cancerous cells. Bioinformatic analysis of the -2500 to +16 bp region of the HOP gene identified a large CpG island and a range of putative cis-elements. Many of the cis-elements were potentially bound by transcription factors which are activated by oncogenic pathways. Luciferase reporter assays demonstrated that the upstream region of the HOP gene contains an active promoter in vitro. Truncation of this region suggested that the core HOP promoter region was -855 to +16 bp. HOP promoter activity was highest in Hs578T, HEK293T and SV40- transformed MEF1 cell lines which expressed mutant or inactive p53. In a mutant p53 background, expression of wild-type p53 led to a reduction in promoter activity, while inhibition of wild-type p53 in HeLa cells increased HOP promoter activity. Additionally, in Hs578T and HEK293T cell lines containing inactive p53, expression of HRAS increased HOP promoter activity. However, HRAS activation of the HOP promoter was inhibited by p53 overexpression. These findings suggest for the first time that HOP expression in cancer may be regulated by both RAS activation and p53 inhibition. Taken together, these data suggest that HOP may be part of the cancer gene signature induced by a combination of mutant p53 and mutated RAS that is associated with cellular transformation.
- Format
- 11 pages
- Format
- Language
- English
- Relation
- Cell Stress and Chaperones
- Relation
- Mattison, Stacey A., Blatch, Gregory L., Edkins, Adrienne L. (2017) HOP expression is regulated by p53 and RAS and characteristic of a cancer gene signature. Cell Stress and Chaperones, 2017, 22 (2), p.213 - 223. https://doi.org/10.1007/s12192-016-0755-8
- Relation
- Cell Stress and Chaperones volume 22 number 2 213 223 March 2017 1466-1268
- Rights
- Springer Nature
- Rights
- Use of this resource is governed by the terms and conditions of the National Library of South Africa Copyright Act (http://www.nlsa.ac.za/downloads/Copyright Act.pdf
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RU DST/NRF SARChI for Molecular and Cellular Biology of the Eukaryotic Stress Response
Edkins, Adrienne Lesley (Associate Prof)
Blatch, Gregory Lloyd (Prof)
RU Centre for Chemico- and Biomedicinal Research (CCBR)
RU Department of Biochemistry, Microbiology and Bioinformatics
SDG 03. Good Health and Well-Being
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