p21-activated kinase 3 (PAK3) is an AP-1 regulated gene contributing to actin organisation and migration of transformed fibroblasts

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dc.contributor.authorHolderness-Parker, Ninaen_ZA
dc.contributor.authorDonninger, Howarden_ZA
dc.contributor.authorBirrer, Michael Jen_ZA
dc.contributor.authorLeaner, Virna Den_ZA
dc.date.accessioned2016-01-02T05:07:44Z
dc.date.available2016-01-02T05:07:44Z
dc.date.issued2013en_ZA
dc.description.abstractActivating Protein 1 (AP-1) plays a vital role in cell proliferation, differentiation and apoptosis. While de-regulation of AP-1 has been linked to many cancers, little is known regarding its downstream transcriptional targets that associate with cellular transformation. Previous studies identified 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 investigate 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 expression in cJun/AP-1 over-expressing cells associated with a significant increase in PAK3 promoter activation. This increased promoter activity was lost when a single putative Jun binding site, which can bind AP-1 directly both in vitro and in vivo, was mutated. Further, inhibition of PAK3 using siRNA showed a regression in the cell morphology, migratory potential and actin organisation associated with AP-1 transformed cells. Our study is a first to describe a role for AP-1 in regulating PAK3 expression and suggest that PAK3 is an AP-1 target required for actin organization and migration observed in transformed cells.en_ZA
dc.identifier.apacitationHolderness-Parker, N., Donninger, H., Birrer, M. J., & Leaner, V. D. (2013). p21-activated kinase 3 (PAK3) is an AP-1 regulated gene contributing to actin organisation and migration of transformed fibroblasts. <i>PLoS One</i>, http://hdl.handle.net/11427/16179en_ZA
dc.identifier.chicagocitationHolderness-Parker, Nina, Howard Donninger, Michael J Birrer, and Virna D Leaner "p21-activated kinase 3 (PAK3) is an AP-1 regulated gene contributing to actin organisation and migration of transformed fibroblasts." <i>PLoS One</i> (2013) http://hdl.handle.net/11427/16179en_ZA
dc.identifier.citationParker, N. H., Donninger, H., Birrer, M. J., & Leaner, V. D. (2013). p21-activated kinase 3 (PAK3) is an AP-1 regulated gene contributing to actin organisation and migration of transformed fibroblasts. PLoS ONE, 8(6), e66892. doi:10.1371/journal.pone.0066892en_ZA
dc.identifier.ris TY - Journal Article AU - Holderness-Parker, Nina AU - Donninger, Howard AU - Birrer, Michael J AU - Leaner, Virna D AB - Activating Protein 1 (AP-1) plays a vital role in cell proliferation, differentiation and apoptosis. While de-regulation of AP-1 has been linked to many cancers, little is known regarding its downstream transcriptional targets that associate with cellular transformation. Previous studies identified 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 investigate 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 expression in cJun/AP-1 over-expressing cells associated with a significant increase in PAK3 promoter activation. This increased promoter activity was lost when a single putative Jun binding site, which can bind AP-1 directly both in vitro and in vivo, was mutated. Further, inhibition of PAK3 using siRNA showed a regression in the cell morphology, migratory potential and actin organisation associated with AP-1 transformed cells. Our study is a first to describe a role for AP-1 in regulating PAK3 expression and suggest that PAK3 is an AP-1 target required for actin organization and migration observed in transformed cells. DA - 2013 DB - OpenUCT DO - 10.1371/journal.pone.0066892 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - p21-activated kinase 3 (PAK3) is an AP-1 regulated gene contributing to actin organisation and migration of transformed fibroblasts TI - p21-activated kinase 3 (PAK3) is an AP-1 regulated gene contributing to actin organisation and migration of transformed fibroblasts UR - http://hdl.handle.net/11427/16179 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16179
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0066892
dc.identifier.vancouvercitationHolderness-Parker N, Donninger H, Birrer MJ, Leaner VD. p21-activated kinase 3 (PAK3) is an AP-1 regulated gene contributing to actin organisation and migration of transformed fibroblasts. PLoS One. 2013; http://hdl.handle.net/11427/16179.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Medical Biochemistryen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2013 Holderness Parker et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherSmall interfering RNAsen_ZA
dc.subject.otherFibroblastsen_ZA
dc.subject.otherActinsen_ZA
dc.subject.otherGene expressionen_ZA
dc.subject.otherOligomersen_ZA
dc.subject.otherCell proliferationen_ZA
dc.subject.otherPromoter regionsen_ZA
dc.subject.otherCell migrationen_ZA
dc.titlep21-activated kinase 3 (PAK3) is an AP-1 regulated gene contributing to actin organisation and migration of transformed fibroblastsen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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