Nek10 mediates G2/M cell cycle arrest and MEK autoactivation in response to UV irradiation.

Abstract:

:Appropriate cell cycle checkpoint control is essential for the maintenance of cell and organismal homeostasis. Members of the Nek (NIMA-related kinase) family of serine/threonine protein kinases have been implicated in the regulation of various aspects of the cell cycle. We explored the cellular functions of Nek10, a novel member of the Nek family, and demonstrate a role for Nek10 in the cellular UV response. Nek10 was required for the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling upon UV irradiation but not in response to mitogens, such as epidermal growth factor stimulation. Nek10 physically associated with Raf-1 and MEK1 in a Raf-1-dependent manner, and the formation of this complex was necessary for Nek10-mediated MEK1 activation. Nek10 did not affect the kinase activity of Raf-1 but instead promoted the autophosphorylation-dependent activation of MEK1. The appropriate maintenance of the G(2)/M checkpoint following UV irradiation required Nek10 expression and ERK1/2 activation. Taken together, our results uncover a role for Nek10 in the cellular response to UV irradiation.

journal_name

Mol Cell Biol

authors

Moniz LS,Stambolic V

doi

10.1128/MCB.00648-10

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

30-42

issue

1

eissn

0270-7306

issn

1098-5549

pii

MCB.00648-10

journal_volume

31

pub_type

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