HOP expression is regulated by p53 and RAS and characteristic of a cancer gene signature
- Mattison, Stacey A, Blatch, Gregory L, Edkins, Adrienne L
- Authors: Mattison, Stacey A , Blatch, Gregory L , Edkins, Adrienne L
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66278 , vital:28928 , https://doi.org/10.1007/s12192-016-0755-8
- Description: publisher version , 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.
- Full Text: false
- Date Issued: 2018
- Authors: Mattison, Stacey A , Blatch, Gregory L , Edkins, Adrienne L
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66278 , vital:28928 , https://doi.org/10.1007/s12192-016-0755-8
- Description: publisher version , 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.
- Full Text: false
- Date Issued: 2018
Counting on demographic equity to transform institutional cultures at historically white South African universities?:
- Booi, Masixole, Vincent, Louise, Liccardo, Sabrina
- Authors: Booi, Masixole , Vincent, Louise , Liccardo, Sabrina
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/141946 , vital:38018 , DOI: 10.1080/07294360.2017.1289155
- Description: The post-apartheid higher education transformation project is faced with the challenge of recruiting and retaining black academics and other senior staff. But when we shift the focus from participation rates to equality–inequality within historically white universities (HWUs), then the discourse changes from demographic equity and redress to institutional culture and diversity. HWUs invoke the need to maintain their position as leading higher education institutions globally, and notions of ‘quality’ and ‘excellence’ have emerged as discursive practices, which serve to perpetuate exclusion. The question then arises as to which forms of capital comprise the Gold Standard at HWUs? Several South African universities have responded to the challenge of recruiting and retaining black academics by initiating programmes for the ‘accelerated development’ of these candidates.
- Full Text:
- Date Issued: 2017
- Authors: Booi, Masixole , Vincent, Louise , Liccardo, Sabrina
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/141946 , vital:38018 , DOI: 10.1080/07294360.2017.1289155
- Description: The post-apartheid higher education transformation project is faced with the challenge of recruiting and retaining black academics and other senior staff. But when we shift the focus from participation rates to equality–inequality within historically white universities (HWUs), then the discourse changes from demographic equity and redress to institutional culture and diversity. HWUs invoke the need to maintain their position as leading higher education institutions globally, and notions of ‘quality’ and ‘excellence’ have emerged as discursive practices, which serve to perpetuate exclusion. The question then arises as to which forms of capital comprise the Gold Standard at HWUs? Several South African universities have responded to the challenge of recruiting and retaining black academics by initiating programmes for the ‘accelerated development’ of these candidates.
- Full Text:
- Date Issued: 2017
Russian wheat aphids: Breakfast, lunch, and supper. Feasting on small grains in South Africa
- Botha, Christiaan E J, Sacranie, S, Gallagher, Sean, Hill, Jaclyn M
- Authors: Botha, Christiaan E J , Sacranie, S , Gallagher, Sean , Hill, Jaclyn M
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/69031 , vital:29374 , https://doi.org/10.1016/j.sajb.2016.12.006
- Description: The Russian Wheat Aphid (Diuraphis noxia, RWA) negatively impacts commercially grown barley and wheat in South Africa. Climate change, the attendant rise in [CO2], and the appearance of new RWA biotypes have the potential to induce severe crop yield loss in agriculturally important wheat and barley cultivars. This study presents data showing changes in relative aphid population numbers, concurrently with assessments of plant damage under controlled environmental conditions, under ambient and elevated (450 ppm) [CO2]. Extensive structural damage to the vascular tissue and disruption to the transport systems were revealed using light, fluorescence and electron microscopy. This, coupled with biotype population studies, demonstrated that RWA has the capacity to inflict severe, potentially permanent damage to vegetative small grain plants. Furthermore, some currently ‘resistant’ cultivars may well lose resistance as a direct result of increasing atmospheric [CO2]. A small (50 ppm) increase in atmospheric [CO2] may result in increased aphid population numbers, potentially serious plant damage and, by implication, a potentially negative impact on yield, as increased aphid density per plant leads to an accelerated disruption of the assimilate and transpiration transport pathways. These outcomes pose a direct threat to the commercial small grain industry of South Africa and by extension, to other small grain production areas elsewhere.
- Full Text: false
- Date Issued: 2016
- Authors: Botha, Christiaan E J , Sacranie, S , Gallagher, Sean , Hill, Jaclyn M
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/69031 , vital:29374 , https://doi.org/10.1016/j.sajb.2016.12.006
- Description: The Russian Wheat Aphid (Diuraphis noxia, RWA) negatively impacts commercially grown barley and wheat in South Africa. Climate change, the attendant rise in [CO2], and the appearance of new RWA biotypes have the potential to induce severe crop yield loss in agriculturally important wheat and barley cultivars. This study presents data showing changes in relative aphid population numbers, concurrently with assessments of plant damage under controlled environmental conditions, under ambient and elevated (450 ppm) [CO2]. Extensive structural damage to the vascular tissue and disruption to the transport systems were revealed using light, fluorescence and electron microscopy. This, coupled with biotype population studies, demonstrated that RWA has the capacity to inflict severe, potentially permanent damage to vegetative small grain plants. Furthermore, some currently ‘resistant’ cultivars may well lose resistance as a direct result of increasing atmospheric [CO2]. A small (50 ppm) increase in atmospheric [CO2] may result in increased aphid population numbers, potentially serious plant damage and, by implication, a potentially negative impact on yield, as increased aphid density per plant leads to an accelerated disruption of the assimilate and transpiration transport pathways. These outcomes pose a direct threat to the commercial small grain industry of South Africa and by extension, to other small grain production areas elsewhere.
- Full Text: false
- Date Issued: 2016
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