Analysis of the human HSP70-HSP90 organising protein (HOP) gene - characterisation of the promoter and identification of a novel isoform
- Authors: Mattison, Stacey
- Date: 2018
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/62821 , vital:28296
- Description: Expected release date-April 2020
- Full Text:
- Date Issued: 2018
- Authors: Mattison, Stacey
- Date: 2018
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/62821 , vital:28296
- Description: Expected release date-April 2020
- Full Text:
- Date Issued: 2018
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
Hsp70/Hsp90 organising protein (hop): beyond interactions with chaperones and prion proteins
- Baindur-Hudson, Swati, Edkins, Adrienne L, Blatch, Gregory L
- Authors: Baindur-Hudson, Swati , Edkins, Adrienne L , Blatch, Gregory L
- Date: 2015
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/164852 , vital:41178 , ISBN 978-3-319-11730-0 , DOI: 10.1007/978-3-319-11731-7_3
- Description: The Hsp70/Hsp90 organising protein (Hop), also known as stress-inducible protein 1 (STI1), has received considerable attention for diverse cellular functions in both healthy and diseased states. There is extensive evidence that intracellular Hop is a co-chaperone of the major chaperones Hsp70 and Hsp90, playing an important role in the productive folding of Hsp90 client proteins. Consequently, Hop is implicated in a number of key signalling pathways, including aberrant pathways leading to cancer. However, Hop is also secreted and it is now well established that Hop also serves as a receptor for the prion protein, PrPC.
- Full Text:
- Date Issued: 2015
- Authors: Baindur-Hudson, Swati , Edkins, Adrienne L , Blatch, Gregory L
- Date: 2015
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/164852 , vital:41178 , ISBN 978-3-319-11730-0 , DOI: 10.1007/978-3-319-11731-7_3
- Description: The Hsp70/Hsp90 organising protein (Hop), also known as stress-inducible protein 1 (STI1), has received considerable attention for diverse cellular functions in both healthy and diseased states. There is extensive evidence that intracellular Hop is a co-chaperone of the major chaperones Hsp70 and Hsp90, playing an important role in the productive folding of Hsp90 client proteins. Consequently, Hop is implicated in a number of key signalling pathways, including aberrant pathways leading to cancer. However, Hop is also secreted and it is now well established that Hop also serves as a receptor for the prion protein, PrPC.
- Full Text:
- Date Issued: 2015
Facile synthesis and biological evaluation of assorted indolyl-3-amides and esters from a single, stable carbonyl nitrile intermediate
- Veale, Clinton G L, Edkins, Adrienne L, de la Mare, Jo-Anne, de Kock, Carmen, Smith, Peter J, Khanye, Setshaba D
- Authors: Veale, Clinton G L , Edkins, Adrienne L , de la Mare, Jo-Anne , de Kock, Carmen , Smith, Peter J , Khanye, Setshaba D
- Date: 2015
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66221 , vital:28919 , https://doi.org/10.1016/j.tetlet.2015.02.090
- Description: publisher version , The synthesis of biologically relevant amides and esters is routinely conducted under complex reaction conditions or requires the use of additional catalysts in order to generate sensitive electrophilic species for attack by a nucleophile. Here we present the synthesis of different indolic esters and amides from indolyl-3-carbonyl nitrile, without the requirement of anhydrous reaction conditions or catalysts. Additionally, we screened these compounds for potential in vitro antimalarial and anticancer activity, revealing 1H-indolyl-3-carboxylic acid 3-(indolyl-3-carboxamide)aminobenzyl ester to have moderate activity against both lines.
- Full Text: false
- Date Issued: 2015
- Authors: Veale, Clinton G L , Edkins, Adrienne L , de la Mare, Jo-Anne , de Kock, Carmen , Smith, Peter J , Khanye, Setshaba D
- Date: 2015
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66221 , vital:28919 , https://doi.org/10.1016/j.tetlet.2015.02.090
- Description: publisher version , The synthesis of biologically relevant amides and esters is routinely conducted under complex reaction conditions or requires the use of additional catalysts in order to generate sensitive electrophilic species for attack by a nucleophile. Here we present the synthesis of different indolic esters and amides from indolyl-3-carbonyl nitrile, without the requirement of anhydrous reaction conditions or catalysts. Additionally, we screened these compounds for potential in vitro antimalarial and anticancer activity, revealing 1H-indolyl-3-carboxylic acid 3-(indolyl-3-carboxamide)aminobenzyl ester to have moderate activity against both lines.
- Full Text: false
- Date Issued: 2015
Ferrocenyl and organic novobiocin derivatives: synthesis and their in vitro biological activity
- Mbaba, Mziyanda, Mabhula, Amanda N, Boel, Natasha, Edkins, Adrienne L, Isaacs, Michelle, Hoppe, Heinrich C, Khanye, Setshaba D
- Authors: Mbaba, Mziyanda , Mabhula, Amanda N , Boel, Natasha , Edkins, Adrienne L , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66189 , vital:28914 , https://doi.org/10.1016/j.jinorgbio.2017.04.014
- Description: publisher version , A focused series of novobiocin derivatives containing a ferrocene unit together with their corresponding organic novobiocin analogues have been synthesized in modest to good yields. These compounds were screened for biological activity against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) and human breast cancer cell line (HCC38). With the exception of compounds 5c and 5d, the general trend observed is that incorporation of the ferrocene moiety into novobiocin scaffold resulted in compounds 6a–d/6f showing enhanced activity compared to organic analogues 5a–b and 5e–f.
- Full Text: false
- Date Issued: 2017
- Authors: Mbaba, Mziyanda , Mabhula, Amanda N , Boel, Natasha , Edkins, Adrienne L , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66189 , vital:28914 , https://doi.org/10.1016/j.jinorgbio.2017.04.014
- Description: publisher version , A focused series of novobiocin derivatives containing a ferrocene unit together with their corresponding organic novobiocin analogues have been synthesized in modest to good yields. These compounds were screened for biological activity against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) and human breast cancer cell line (HCC38). With the exception of compounds 5c and 5d, the general trend observed is that incorporation of the ferrocene moiety into novobiocin scaffold resulted in compounds 6a–d/6f showing enhanced activity compared to organic analogues 5a–b and 5e–f.
- Full Text: false
- Date Issued: 2017
Synthesis and evaluation of substituted 4-(N-benzylamino)cinnamate esters as potential anti-cancer agents and HIV-1 integrase inhibitors
- Faridoon, H, Edkins, Adrienne L, Isaacs, Michelle, Mnkandhla, Dumisani, Hoppe, Heinrich C, Kaye, Perry T
- Authors: Faridoon, H , Edkins, Adrienne L , Isaacs, Michelle , Mnkandhla, Dumisani , Hoppe, Heinrich C , Kaye, Perry T
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66289 , vital:28929 , https://doi.org/10.1016/j.bmcl.2016.05.023
- Description: publisher version , Encouraging selectivity and low micromolar activity against HeLa cervical carcinoma (IC50 ⩾ 3.0 μM) and the aggressive MDA-MB-231 triple negative breast carcinoma (IC50 ⩾ 9.6 μM) cell lines has been exhibited by a number of readily accessible 4-(N-benzylamino)cinnamate esters. The potential of the ligands as HIV-1 integrase inhibitors has also been examined.
- Full Text: false
- Date Issued: 2016
- Authors: Faridoon, H , Edkins, Adrienne L , Isaacs, Michelle , Mnkandhla, Dumisani , Hoppe, Heinrich C , Kaye, Perry T
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66289 , vital:28929 , https://doi.org/10.1016/j.bmcl.2016.05.023
- Description: publisher version , Encouraging selectivity and low micromolar activity against HeLa cervical carcinoma (IC50 ⩾ 3.0 μM) and the aggressive MDA-MB-231 triple negative breast carcinoma (IC50 ⩾ 9.6 μM) cell lines has been exhibited by a number of readily accessible 4-(N-benzylamino)cinnamate esters. The potential of the ligands as HIV-1 integrase inhibitors has also been examined.
- Full Text: false
- Date Issued: 2016
The networking of chaperones by co-chaperones: control of cellular protein homeostasis
- Edkins, Adrienne L, Blatch, Gregory L
- Authors: Edkins, Adrienne L , Blatch, Gregory L
- Date: 2014
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/165107 , vital:41209 , ISBN 978-3-319-11731-7
- Description: Co-chaperones are important mediators of the outcome of chaperone assisted protein homeostasis, which is a dynamic balance between the integrated processes of protein folding, degradation and translocation. The Networking of Chaperones by Co-chaperones describes how the function of the major molecular chaperones is regulated by a cohort of diverse non-client proteins, known as co-chaperones. The second edition includes the current status of the field and descriptions of a number of novel co-chaperones that have been recently identified. This new edition has a strong focus on the role of co-chaperones in human disease and as putative drug targets. The book will be a resource for both newcomers and established researchers in the field of cell stress and chaperones, as well as those interested in cross-cutting disciplines such as cellular networks and systems biology.
- Full Text:
- Date Issued: 2014
- Authors: Edkins, Adrienne L , Blatch, Gregory L
- Date: 2014
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/165107 , vital:41209 , ISBN 978-3-319-11731-7
- Description: Co-chaperones are important mediators of the outcome of chaperone assisted protein homeostasis, which is a dynamic balance between the integrated processes of protein folding, degradation and translocation. The Networking of Chaperones by Co-chaperones describes how the function of the major molecular chaperones is regulated by a cohort of diverse non-client proteins, known as co-chaperones. The second edition includes the current status of the field and descriptions of a number of novel co-chaperones that have been recently identified. This new edition has a strong focus on the role of co-chaperones in human disease and as putative drug targets. The book will be a resource for both newcomers and established researchers in the field of cell stress and chaperones, as well as those interested in cross-cutting disciplines such as cellular networks and systems biology.
- Full Text:
- Date Issued: 2014
STAT3 interacts directly with Hsp90:
- Prinsloo, Earl, Kramer, Adam H, Edkins, Adrienne L, Blatch, Gregory L
- Authors: Prinsloo, Earl , Kramer, Adam H , Edkins, Adrienne L , Blatch, Gregory L
- Date: 2012
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165142 , vital:41212 , DOI: 10.1002/iub.607
- Description: Heat shock protein 90 (Hsp90) functionally modulates signal transduction. The signal transducer and activator of transcription 3 (STAT3) mediates interleukin‐6 family cytokine signaling. Aberrant activation and mutation of STAT3 is associated with oncogenesis and immune disorders, respectively. Hsp90 and STAT3 have previously been shown to colocalize and coimmunoprecipitate in common complexes.
- Full Text:
- Date Issued: 2012
- Authors: Prinsloo, Earl , Kramer, Adam H , Edkins, Adrienne L , Blatch, Gregory L
- Date: 2012
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165142 , vital:41212 , DOI: 10.1002/iub.607
- Description: Heat shock protein 90 (Hsp90) functionally modulates signal transduction. The signal transducer and activator of transcription 3 (STAT3) mediates interleukin‐6 family cytokine signaling. Aberrant activation and mutation of STAT3 is associated with oncogenesis and immune disorders, respectively. Hsp90 and STAT3 have previously been shown to colocalize and coimmunoprecipitate in common complexes.
- Full Text:
- Date Issued: 2012
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
General structural and functional features of molecular chaperones:
- Edkins, Adrienne L, Boshoff, Aileen
- Authors: Edkins, Adrienne L , Boshoff, Aileen
- Date: 2014
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/164808 , vital:41174 , ISBN 978-94-007-7437-7 , DOI: 10.1007/978-94-007-7438-4_2
- Description: Molecular chaperones are a group of structurally diverse and highly conserved ubiquitous proteins. They play crucial roles in facilitating the correct folding of proteins in vivo by preventing protein aggregation or facilitating the appropriate folding and assembly of proteins. Heat shock proteins form the major class of molecular chaperones that are responsible for protein folding events in the cell. This is achieved by ATP-dependent (folding machines) or ATP-independent mechanisms (holders). Heat shock proteins are induced by a variety of stresses, besides heat shock. The large and varied heat shock protein class is categorised into several subfamilies based on their sizes in kDa namely, small Hsps (HSPB), Hsp40 (DNAJ), Hsp60 (HSPD/E; Chaperonins), Hsp70 (HSPA), Hsp90 (HSPC), and Hsp100.
- Full Text:
- Date Issued: 2014
- Authors: Edkins, Adrienne L , Boshoff, Aileen
- Date: 2014
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/164808 , vital:41174 , ISBN 978-94-007-7437-7 , DOI: 10.1007/978-94-007-7438-4_2
- Description: Molecular chaperones are a group of structurally diverse and highly conserved ubiquitous proteins. They play crucial roles in facilitating the correct folding of proteins in vivo by preventing protein aggregation or facilitating the appropriate folding and assembly of proteins. Heat shock proteins form the major class of molecular chaperones that are responsible for protein folding events in the cell. This is achieved by ATP-dependent (folding machines) or ATP-independent mechanisms (holders). Heat shock proteins are induced by a variety of stresses, besides heat shock. The large and varied heat shock protein class is categorised into several subfamilies based on their sizes in kDa namely, small Hsps (HSPB), Hsp40 (DNAJ), Hsp60 (HSPD/E; Chaperonins), Hsp70 (HSPA), Hsp90 (HSPC), and Hsp100.
- Full Text:
- Date Issued: 2014
In vitro and in vivo toxicity assessment of biologically synthesized silver nanoparticles from Elaeodendron croceum:
- Odeyemi, S W, de la Mare, Jo-Anne, Edkins, Adrienne L, Afolayan, A J
- Authors: Odeyemi, S W , de la Mare, Jo-Anne , Edkins, Adrienne L , Afolayan, A J
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163488 , vital:41042 , DOI: 10.1515/jcim-2018-0184
- Description: The cytotoxic properties of nanoparticles have attracted a great deal of attention in the field of nanoscience and nanotechnology due to their small size and ability to penetrate cellular membranes.
- Full Text:
- Date Issued: 2019
- Authors: Odeyemi, S W , de la Mare, Jo-Anne , Edkins, Adrienne L , Afolayan, A J
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163488 , vital:41042 , DOI: 10.1515/jcim-2018-0184
- Description: The cytotoxic properties of nanoparticles have attracted a great deal of attention in the field of nanoscience and nanotechnology due to their small size and ability to penetrate cellular membranes.
- Full Text:
- Date Issued: 2019
Hop depletion reduces HSF1 levels and activity and coincides with reduced stress resilience:
- Chakraborty, Abantika, Edkins, Adrienne L
- Authors: Chakraborty, Abantika , Edkins, Adrienne L
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165440 , vital:41244 , https://doi.org/10.1016/j.bbrc.2020.04.072
- Description: Heat-shock factor 1 (HSF1) regulates the transcriptional response to stress and controls expression of molecular chaperones required for cell survival. Here we report that HSF1 is regulated by the abundance of the Hsp70-Hsp90 organizing protein (Hop/STIP1).
- Full Text:
- Date Issued: 2020
- Authors: Chakraborty, Abantika , Edkins, Adrienne L
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165440 , vital:41244 , https://doi.org/10.1016/j.bbrc.2020.04.072
- Description: Heat-shock factor 1 (HSF1) regulates the transcriptional response to stress and controls expression of molecular chaperones required for cell survival. Here we report that HSF1 is regulated by the abundance of the Hsp70-Hsp90 organizing protein (Hop/STIP1).
- Full Text:
- Date Issued: 2020
CHIP: a co-chaperone for degradation by the proteasome
- Authors: Edkins, Adrienne L
- Date: 2015
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/164863 , vital:41179 , ISBN 978-3-319-11730-0 , DOI: 10.1007/978-3-319-11731-7_11
- Description: Protein homeostasis relies on a balance between protein folding and protein degradation. Molecular chaperones like Hsp70 and Hsp90 fulfil well-defined roles in protein folding and conformational stability via ATP dependent reaction cycles. These folding cycles are controlled by associations with a cohort of non-client protein co-chaperones, such as Hop, p23 and Aha1. Pro-folding co-chaperones facilitate the transit of the client protein through the chaperone mediated folding process. However, chaperones are also involved in ubiquitin-mediated proteasomal degradation of client proteins. Similar to folding complexes, the ability of chaperones to mediate protein degradation is regulated by co-chaperones, such as the C terminal Hsp70 binding protein (CHIP).
- Full Text:
- Date Issued: 2015
- Authors: Edkins, Adrienne L
- Date: 2015
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/164863 , vital:41179 , ISBN 978-3-319-11730-0 , DOI: 10.1007/978-3-319-11731-7_11
- Description: Protein homeostasis relies on a balance between protein folding and protein degradation. Molecular chaperones like Hsp70 and Hsp90 fulfil well-defined roles in protein folding and conformational stability via ATP dependent reaction cycles. These folding cycles are controlled by associations with a cohort of non-client protein co-chaperones, such as Hop, p23 and Aha1. Pro-folding co-chaperones facilitate the transit of the client protein through the chaperone mediated folding process. However, chaperones are also involved in ubiquitin-mediated proteasomal degradation of client proteins. Similar to folding complexes, the ability of chaperones to mediate protein degradation is regulated by co-chaperones, such as the C terminal Hsp70 binding protein (CHIP).
- Full Text:
- Date Issued: 2015
Regulation of Kaposi’s Sarcoma-Associated Herpesvirus Biology by Host Molecular Chaperones:
- Kirigin, Elisa, Ruck, Duncan Kyle, Jackson, Zoe, Murphy, James, McDonnell, Euan, Okpara, Michael O, Whitehouse, Adrian, Edkins, Adrienne L
- Authors: Kirigin, Elisa , Ruck, Duncan Kyle , Jackson, Zoe , Murphy, James , McDonnell, Euan , Okpara, Michael O , Whitehouse, Adrian , Edkins, Adrienne L
- Date: 2020
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/165385 , vital:41239 , ISBN , https://0-doi.org.wam.seals.ac.za/10.1007/7515_2020_18
- Description: Kaposi’s sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus associated with development of the human diseases Kaposi’s sarcoma, Primary Effusion Lymphoma and Multicentric Castleman’s Disease. KSHV establishes a chronic latent infection in hosts, with periods of viral lytic replication, where both latent and lytic virus cycles contribute to malignancy, most often in the immunodeficient host.
- Full Text:
- Date Issued: 2020
- Authors: Kirigin, Elisa , Ruck, Duncan Kyle , Jackson, Zoe , Murphy, James , McDonnell, Euan , Okpara, Michael O , Whitehouse, Adrian , Edkins, Adrienne L
- Date: 2020
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/165385 , vital:41239 , ISBN , https://0-doi.org.wam.seals.ac.za/10.1007/7515_2020_18
- Description: Kaposi’s sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus associated with development of the human diseases Kaposi’s sarcoma, Primary Effusion Lymphoma and Multicentric Castleman’s Disease. KSHV establishes a chronic latent infection in hosts, with periods of viral lytic replication, where both latent and lytic virus cycles contribute to malignancy, most often in the immunodeficient host.
- Full Text:
- Date Issued: 2020
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
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
Dynamic mitochondrial localisation of STAT3 in the cellular adipogenesis model 3T3-L1:
- Kramer, Adam H, Edkins, Adrienne L, Hoppe, Heinrich C, Prinsloo, Earl
- Authors: Kramer, Adam H , Edkins, Adrienne L , Hoppe, Heinrich C , Prinsloo, Earl
- Date: 2015
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164885 , vital:41181 , DOI: 10.1002/jcb.25076
- Description: A mechanistic relationship exists between protein localisation, activity and cellular differentiation. Understanding the contribution of these molecular mechanisms is required for elucidation of conditions that drive development. Literature suggests non‐canonical translocation of the Signal Transducer and Activator of Transcription 3 (STAT3) to the mitochondria contributes to the regulation of the electron transport chain, cellular respiration and reactive oxygen species production. Based on this we investigated the role of mitochondrial STAT3, specifically the serine 727 phosphorylated form, in cellular differentiation using the well‐defined mouse adipogenic model 3T3-L1.
- Full Text:
- Date Issued: 2015
- Authors: Kramer, Adam H , Edkins, Adrienne L , Hoppe, Heinrich C , Prinsloo, Earl
- Date: 2015
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164885 , vital:41181 , DOI: 10.1002/jcb.25076
- Description: A mechanistic relationship exists between protein localisation, activity and cellular differentiation. Understanding the contribution of these molecular mechanisms is required for elucidation of conditions that drive development. Literature suggests non‐canonical translocation of the Signal Transducer and Activator of Transcription 3 (STAT3) to the mitochondria contributes to the regulation of the electron transport chain, cellular respiration and reactive oxygen species production. Based on this we investigated the role of mitochondrial STAT3, specifically the serine 727 phosphorylated form, in cellular differentiation using the well‐defined mouse adipogenic model 3T3-L1.
- Full Text:
- Date Issued: 2015
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
Expanding the SAR of Nontoxic Antiplasmodial Indolyl-3-ethanone Ethers and Thioethers:
- Lunga, Mayibongwe J, Chisango, Ruramai L, Weyers, Carli, Isaacs, Michelle, Taylor, Dale, Edkins, Adrienne L, Khanye, Setshaba D, Hoppe, Heinrich C, Veale, Clinton G L
- Authors: Lunga, Mayibongwe J , Chisango, Ruramai L , Weyers, Carli , Isaacs, Michelle , Taylor, Dale , Edkins, Adrienne L , Khanye, Setshaba D , Hoppe, Heinrich C , Veale, Clinton G L
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164389 , vital:41114 , DOI: 10.1002/cmdc.201800235
- Description: Despite major strides in reducing Plasmodium falciparum infections, this parasite still accounts for roughly half a million annual deaths. This problem is compounded by the decreased efficacy of artemisinin combination therapies. Therefore, the development and optimisation of novel antimalarial chemotypes is critical. In this study, we describe our strategic approach to optimise a class of previously reported antimalarials, resulting in the discovery of 1-(5-chloro-1H-indol-3-yl)-2-[(4-cyanophenyl)thio]ethanone (13) and 1-(5-chloro-1H-indol-3-yl)-2-[(4-nitrophenyl)thio]ethanone (14), whose activity was equipotent to that of chloroquine against the P. falciparum 3D7 strain.
- Full Text:
- Date Issued: 2018
- Authors: Lunga, Mayibongwe J , Chisango, Ruramai L , Weyers, Carli , Isaacs, Michelle , Taylor, Dale , Edkins, Adrienne L , Khanye, Setshaba D , Hoppe, Heinrich C , Veale, Clinton G L
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164389 , vital:41114 , DOI: 10.1002/cmdc.201800235
- Description: Despite major strides in reducing Plasmodium falciparum infections, this parasite still accounts for roughly half a million annual deaths. This problem is compounded by the decreased efficacy of artemisinin combination therapies. Therefore, the development and optimisation of novel antimalarial chemotypes is critical. In this study, we describe our strategic approach to optimise a class of previously reported antimalarials, resulting in the discovery of 1-(5-chloro-1H-indol-3-yl)-2-[(4-cyanophenyl)thio]ethanone (13) and 1-(5-chloro-1H-indol-3-yl)-2-[(4-nitrophenyl)thio]ethanone (14), whose activity was equipotent to that of chloroquine against the P. falciparum 3D7 strain.
- Full Text:
- Date Issued: 2018
Targeting conserved pathways as a strategy for novel drug development: disabling the cellular stress response:
- Edkins, Adrienne L, Blatch, Gregory L
- Authors: Edkins, Adrienne L , Blatch, Gregory L
- Date: 2012
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/165129 , vital:41211 , ISBN 978-3-642-28174-7 , DOI: 10.1007/978-3-642-28175-4_4
- Description: The ability to respond to and cope with stress at a molecular level is essential for cell survival. The stress response is conserved across organisms by the expression of a group of molecular chaperones known as heat shock proteins (HSP). HSP are ubiquitous and highly conserved proteins that regulate cellular protein homeostasis and trafficking under physiological and stressful conditions, including diseases such as cancer and malaria. HSP are good drug targets for the treatment of human diseases, as the significant functional and structural data available suggest that they are essential for cell survival and that, despite conservation across species, there are biophysical and biochemical differences between HSP in normal and disease states that allow HSP to be selectively targeted. In this chapter, we review the international status of this area of research and highlight progress by us and other African researchers towards the characterisation and targeting of HSP from humans and parasites from Plasmodium and Trypanosoma as drug targets.
- Full Text:
- Date Issued: 2012
- Authors: Edkins, Adrienne L , Blatch, Gregory L
- Date: 2012
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/165129 , vital:41211 , ISBN 978-3-642-28174-7 , DOI: 10.1007/978-3-642-28175-4_4
- Description: The ability to respond to and cope with stress at a molecular level is essential for cell survival. The stress response is conserved across organisms by the expression of a group of molecular chaperones known as heat shock proteins (HSP). HSP are ubiquitous and highly conserved proteins that regulate cellular protein homeostasis and trafficking under physiological and stressful conditions, including diseases such as cancer and malaria. HSP are good drug targets for the treatment of human diseases, as the significant functional and structural data available suggest that they are essential for cell survival and that, despite conservation across species, there are biophysical and biochemical differences between HSP in normal and disease states that allow HSP to be selectively targeted. In this chapter, we review the international status of this area of research and highlight progress by us and other African researchers towards the characterisation and targeting of HSP from humans and parasites from Plasmodium and Trypanosoma as drug targets.
- Full Text:
- Date Issued: 2012