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 Bioljournal_title
Molecular and cellular biologyauthors
Alexander K,Yang HS,Hinds PWdoi
10.1128/mcb.24.7.2808-2819.2004subject
Has Abstractpub_date
2004-04-01 00:00:00pages
2808-19issue
7eissn
0270-7306issn
1098-5549journal_volume
24pub_type
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