Cellular senescence requires CDK5 repression of Rac1 activity
Cellular senescence requires CDK5 repression of Rac1 activity
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DOI：
10.1128/mcb.24.7.2808-2819.2004
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发表时间：
2004-04-01
影响因子：
5.3
通讯作者：
Hinds, PW
中科院分区：
文献类型：
--
作者：
Alexander, K;Yang, HS;Hinds, PW
细胞衰老是一种肿瘤抑制过程，其特征在于不可逆的细胞周期退出、独特的形态和衰老相关的β-半乳糖苷酶（SA-β-Gal）的表达。我们在此报告CDK 5在诱导衰老细胞骨架变化中的作用。CDK 5活化在衰老细胞中上调。CDK 5活性的增加进一步降低了GTdR α Rac 1活性和Pak活化。衰老表型的表达需要CDK 5对GTCRac 1活性的抑制。Rac 1活性的CDK 5调节对于伴随衰老形态的肌动蛋白聚合是必要的，所述衰老形态响应于pRb、活化Ras的表达或连续传代。抑制CDK 5减弱SA-P-Gal表达并阻断肌动蛋白聚合。这些结果表明，CDK 5在调节Rac 1活性衰老中具有独特的非神经元作用，阐明了诱导衰老和衰老形状变化的机制。
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-P-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.