Cellular Senescence Requires CDK5 Repression of Rac1 Activity

AUTOR(ES)

Alexander, Kamilah

FONTE

American Society for Microbiology

RESUMO

Cellular senescence is a tumor-suppressive process characterized by an irreversible cell cycle exit, a unique morphology, and expression of senescence-associated β-galactosidase (SA-β-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-β-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.

Documentos Relacionados

• Cortactin Tyrosine Phosphorylation Requires Rac1 Activity and Association with the Cortical Actin Cytoskeleton
• The Insert Region of Rac1 Is Essential for Membrane Ruffling but Not Cellular Transformation
• Cdk5 Regulates the Organization of Nestin and Its Association with p35
• Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects
• A Cdk5 inhibitory peptide reduces tau hyperphosphorylation and apoptosis in neurons