CDK5 is a major regulator of the tumor suppressor DLC1

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Item Type:	Article
Title:	CDK5 is a major regulator of the tumor suppressor DLC1
Creators Name:	Tripathi, B.K., Qian, X., Mertins, P., Wang, D., Papageorge, A.G., Carr, S.A. and Lowy, D.R.
Abstract:	DLC1 is a tumor suppressor protein whose full activity depends on its presence at focal adhesions, its Rho-GTPase activating protein (Rho-GAP) function, and its ability to bind several ligands, including tensin and talin. However, the mechanisms that regulate and coordinate these activities remain poorly understood. Here we identify CDK5, a predominantly cytoplasmic serine/threonine kinase, as an important regulator of DLC1 functions. The CDK5 kinase phosphorylates four serines in DLC1 located N-terminal to the Rho-GAP domain. When not phosphorylated, this N-terminal region functions as an autoinhibitory domain that places DLC1 in a closed, inactive conformation by efficiently binding to the Rho-GAP domain. CDK5 phosphorylation reduces this binding and orchestrates the coordinate activation DLC1, including its localization to focal adhesions, its Rho-GAP activity, and its ability to bind tensin and talin. In cancer, these anti-oncogenic effects of CDK5 can provide selective pressure for the down-regulation of DLC1, which occurs frequently in tumors, and can contribute to the pro-oncogenic activity of CDK5 in lung adenocarcinoma.
Keywords:	Amino Acid Sequence, Amino Acid Substitution, Cyclin-Dependent Kinase 5, Focal Adhesions, GTPase-Activating Proteins, HEK293 Cells, Molecular Sequence Data, Phosphorylation, Post-Translational Protein Processing, Protein Binding, Protein Interaction Domains and Motifs, Protein Transport, Tumor Cell Line, Tumor Suppressor Proteins, Animals, Mice
Source:	Journal of Cell Biology
ISSN:	0021-9525
Publisher:	Rockefeller University Press
Volume:	207
Number:	5
Page Range:	627-642
Date:	8 December 2014
Official Publication:	https://doi.org/10.1083/jcb.201405105
PubMed:	View item in PubMed

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