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

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...

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Autores principales:	Nina Holderness Parker, Howard Donninger, Michael J Birrer, Virna D Leaner
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9d5ce22a55ad40afb30df2dc8398cc9f
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spelling	oai:doaj.org-article:9d5ce22a55ad40afb30df2dc8398cc9f2021-11-18T07:40:56Zp21-activated kinase 3 (PAK3) is an AP-1 regulated gene contributing to actin organisation and migration of transformed fibroblasts.1932-620310.1371/journal.pone.0066892https://doaj.org/article/9d5ce22a55ad40afb30df2dc8398cc9f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23818969/?tool=EBIhttps://doaj.org/toc/1932-6203Activating 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.Nina Holderness ParkerHoward DonningerMichael J BirrerVirna D LeanerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e66892 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nina Holderness Parker Howard Donninger Michael J Birrer Virna D Leaner p21-activated kinase 3 (PAK3) is an AP-1 regulated gene contributing to actin organisation and migration of transformed fibroblasts.
description	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.
format	article
author	Nina Holderness Parker Howard Donninger Michael J Birrer Virna D Leaner
author_facet	Nina Holderness Parker Howard Donninger Michael J Birrer Virna D Leaner
author_sort	Nina Holderness Parker
title	p21-activated kinase 3 (PAK3) is an AP-1 regulated gene contributing to actin organisation and migration of transformed fibroblasts.
title_short	p21-activated kinase 3 (PAK3) is an AP-1 regulated gene contributing to actin organisation and migration of transformed fibroblasts.
title_full	p21-activated kinase 3 (PAK3) is an AP-1 regulated gene contributing to actin organisation and migration of transformed fibroblasts.
title_fullStr	p21-activated kinase 3 (PAK3) is an AP-1 regulated gene contributing to actin organisation and migration of transformed fibroblasts.
title_full_unstemmed	p21-activated kinase 3 (PAK3) is an AP-1 regulated gene contributing to actin organisation and migration of transformed fibroblasts.
title_sort	p21-activated kinase 3 (pak3) is an ap-1 regulated gene contributing to actin organisation and migration of transformed fibroblasts.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9d5ce22a55ad40afb30df2dc8398cc9f
work_keys_str_mv	AT ninaholdernessparker p21activatedkinase3pak3isanap1regulatedgenecontributingtoactinorganisationandmigrationoftransformedfibroblasts AT howarddonninger p21activatedkinase3pak3isanap1regulatedgenecontributingtoactinorganisationandmigrationoftransformedfibroblasts AT michaeljbirrer p21activatedkinase3pak3isanap1regulatedgenecontributingtoactinorganisationandmigrationoftransformedfibroblasts AT virnadleaner p21activatedkinase3pak3isanap1regulatedgenecontributingtoactinorganisationandmigrationoftransformedfibroblasts
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p21-activated kinase 3 (PAK3) is an AP-1 regulated gene contributing to actin organisation and migration of transformed fibroblasts.

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