American Society for Biochemistry and Molecular Biology:9650 Rockville Pike:Bethesda, MD 20814:(301)530-7145, EMAIL: [email protected], INTERNET: http://www.faseb.org/asbmb, Fax: (301)571-1824
Abstract
p21CIP1/WAF1 belongs to the CIP/KIP family of Cdk inhibitors,
and its expression is tightly controlled during the cell cycle,
mainly by transcriptional and post-translational mechanisms.
Fine regulation of p21CIP1/WAF1 levels is critical for cell cycle
control and for cellular response to stress. In the present work,
we describe a novel mechanism to modulate p21CIP1/WAF1 levels
mediated by the human GTSE-1 (G2 and S phase-expressed-1)
protein. Our results provide evidence that hGTSE-1 protects
p21CIP1/WAF1 from proteasome-dependent degradation as part
of a functional complex containing the Hsp90-bindingTPRprotein
WISp39. We further show that the hGTSE-1 N-terminal
portion is sufficient for p21CIP1/WAF1 binding and stabilization.
Finally, we demonstrate that hGTSE-1 mediated-p21CIP1/WAF1
stabilization is clearly involved in the ability of cells to counteract
cytotoxicity induced by the microtubule poison paclitaxel
