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Plos One : P21-activated Kinase 3 Pak3 is an Ap-1 Regulated Gene Contributing to Actin Organisation and Migration of Transformed Fibroblasts, Volume 8

By Olson, Michael, F.

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Book Id: WPLBN0003964369
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : P21-activated Kinase 3 Pak3 is an Ap-1 Regulated Gene Contributing to Actin Organisation and Migration of Transformed Fibroblasts, Volume 8  
Author: Olson, Michael, F.
Volume: Volume 8
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection (Contemporary)
Historic
Publication Date:
Publisher: Plos

Description
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-overexpressing Rat1a fibroblasts, as well as in transformed human fibroblasts. Elevated PAK3 expression in cJun/AP-1 overexpressing 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.

 

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