Cellular senescence requires CDK5 repression of Rac1 activity.

Abstract:

:Cellular senescence is a tumor-suppressive process characterized by an irreversible cell cycle exit, a unique morphology, and expression of senescence-associated beta-galactosidase (SA-beta-Gal). We report here a role for CDK5 in induction of senescent cytoskeletal changes. CDK5 activation is upregulated in senescing cells. The increased activity of CDK5 further reduces GTPase Rac1 activity and Pak activation. The repression of the activity of the GTPase Rac1 by CDK5 is required for expression of the senescent phenotype. CDK5 regulation of Rac1 activity is necessary for actin polymerization accompanying senescent morphology in response to expression of pRb, activated Ras, or continuous passage. Inhibition of CDK5 attenuates SA-beta-Gal expression and blocks actin polymerization. These results point to a unique, nonneuronal role for CDK5 in regulation of Rac1 activity in senescence, illuminating the mechanisms underlying induction of senescence and the senescent shape change.

journal_name

Mol Cell Biol

authors

Alexander K,Yang HS,Hinds PW

doi

10.1128/mcb.24.7.2808-2819.2004

subject

Has Abstract

pub_date

2004-04-01 00:00:00

pages

2808-19

issue

7

eissn

0270-7306

issn

1098-5549

journal_volume

24

pub_type

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