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Characterizing the role of p21-Activated Kinase 3 (PAK3) in AP-1-induced transformation
Includes bibliographical references.
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
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Division of Medical Biochemistry
2014
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| _version_ | 1867613278655479808 |
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| access_status_str | Open Access |
| author | Holderness-Parker, Nina Alison Victoria |
| author2 | Leaner, Virna |
| author_browse | Holderness-Parker, Nina Alison Victoria Leaner, Virna |
| author_facet | Leaner, Virna Holderness-Parker, Nina Alison Victoria |
| author_sort | Holderness-Parker, Nina Alison Victoria |
| collection | Thesis |
| description | Includes bibliographical references. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/8709 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:33:35.758Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2014 |
| publishDateRange | 2014 |
| publishDateSort | 2014 |
| publisher | Division of Medical Biochemistry |
| publisherStr | Division of Medical Biochemistry |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/8709 Characterizing the role of p21-Activated Kinase 3 (PAK3) in AP-1-induced transformation Holderness-Parker, Nina Alison Victoria Leaner, Virna Includes bibliographical references. Previous studies identified p21-Activated Kinase 3 (PAK3), a serine/threonine kinase, as a potential AP-1 target gene. PAK3 has been implicated in a variety of pathological disorders and over-expression of other PAK-family members has been linked to cancer. In this study, we investigated AP-1 regulation of PAK3 expression and the role of PAK3 in cJun/AP-1-associated cellular transformation. Our results showed elevated PAK3 expression at both the mRNA and protein level in cJun-over-expressing Rat1a fibroblasts, as well as in transformed human fibroblasts. Elevated PAK3 protein levels were also seen in cervical, ovarian, oesophageal and breast cancer cells lines, while poor survival tracked with high PAK3 expression in ovarian cancer patient material. Elevated PAK3 levels appear to play no role in the proliferation of transformed or cancerous cells, however appears vital for the transformed morphology and actin distribution. These cytoskeletal changes seem to be the underlying force governing cellular migration, as inhibition of PAK3 significantly reduced the motility of both transformed fibroblasts and cancer cell lines. Our data shows that elevated PAK3 expression in response to AP-1 over-expression is regulated through the transcriptional activation of the PAK3 promoter by AP-1 binding directly to a single site in the promoter. We also show that constitutive activation of PAK3 results in changes in cJun phosphorylation and an increase in AP-1 activity, which can be inhibited by a serine/threonine kinase inhibitor. PAK3 and AP-1 proteins were also shown to directly interact with each other. Our study is a first to describe a role for AP-1 in regulating PAK3 expression, and PAK3 in regulating AP-1 activity, identifying a potential feedback loop in which PAK3 is an AP-1 target required for cytoskeletal reorganization and migration observed in transformed cells. 2014-10-21T13:52:44Z 2014-10-21T13:52:44Z 2014 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/8709 eng application/pdf Division of Medical Biochemistry Faculty of Health Sciences University of Cape Town |
| spellingShingle | Holderness-Parker, Nina Alison Victoria Characterizing the role of p21-Activated Kinase 3 (PAK3) in AP-1-induced transformation |
| thesis_degree_str | Doctoral |
| title | Characterizing the role of p21-Activated Kinase 3 (PAK3) in AP-1-induced transformation |
| title_full | Characterizing the role of p21-Activated Kinase 3 (PAK3) in AP-1-induced transformation |
| title_fullStr | Characterizing the role of p21-Activated Kinase 3 (PAK3) in AP-1-induced transformation |
| title_full_unstemmed | Characterizing the role of p21-Activated Kinase 3 (PAK3) in AP-1-induced transformation |
| title_short | Characterizing the role of p21-Activated Kinase 3 (PAK3) in AP-1-induced transformation |
| title_sort | characterizing the role of p21 activated kinase 3 pak3 in ap 1 induced transformation |
| url | http://hdl.handle.net/11427/8709 |
| work_keys_str_mv | AT holdernessparkerninaalisonvictoria characterizingtheroleofp21activatedkinase3pak3inap1inducedtransformation |