Phosphorylation of P62 by Cdk1 Controls the Timely Transit of Cells Through Mitosis and Tumor Cell Proliferation

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2010 Oct 27

PMID 20974803

Citations 46

Authors

Juan F Linares

Ramars Amanchy

Kenneth Greis

Maria T Diaz-Meco

Jorge Moscat

Affiliations

Soon will be listed here.

Abstract

The protein scaffold and signaling regulator p62 is important in critical cellular functions, including bone homeostasis, obesity, and cancer, because of its interactions with various signaling intermediaries. p62 is overexpressed in human cancers and is induced during cell transformation. Its genetic ablation inhibits lung tumorigenesis in vivo and cell proliferation in culture by regulating the TRAF6/NF-κB signaling cascade to control reactive oxygen species (ROS) production and apoptosis. Here we show that cdk1 phosphorylates p62 in vitro and in vivo at T269 and S272, which is necessary for the maintenance of appropriate cyclin B1 levels and the levels of cdk1 activity necessary to allow cells to properly enter and exit mitosis. The lack of cdk1-mediated phosphorylation of p62 leads to a faster exit from mitosis, which translates into enhanced cell proliferation and tumorigenesis in response to Ras-induced transformation. Therefore, p62 emerges as a node for the control of not only cell survival but also cell transit through mitosis.

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