GSK-3? targets Cdc25A for ubiquitin-mediated proteolysis and GSK-3? inactivation leads to Cdc25A overproduction in human cancers

ASIAIR > College of Medical and Health Science > Department of Biotechnology > Journal Article > Item 310904400/4573

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Title:	GSK-3? targets Cdc25A for ubiquitin-mediated proteolysis and GSK-3? inactivation leads to Cdc25A overproduction in human cancers
Authors:	Kang, T.;Wei, Y.;Honaker, Y.;Yamaguchi, H.;Appella, E.;Mien-Chie Hung;Piwnica-Worms, H.
Keywords:	CELLCYCLE;SIGNALING
Date:	2008
Issue Date:	2009-11-27 05:56:53 (UTC+0)
Publisher:	Asia University
Abstract:	The Cdc25A phosphatase positively regulates cell-cycle transitions, is degraded by the proteosome throughout interphase and in response to stress, and is overproduced in human cancers. The kinases targeting Cdc25A for proteolysis during early cell-cycle phases have not been identified, and mechanistic insight into the cause of Cdc25A overproduction in human cancers is lacking. Here, we demonstrate that glycogen synthase kinase-3beta (GSK-3beta) phosphorylates Cdc25A to promote its proteolysis in early cell-cycle phases. Phosphorylation by GSK-3beta requires priming of Cdc25A, and this can be catalyzed by polo-like kinase 3 (Plk-3). Importantly, a strong correlation between Cdc25A overproduction and GSK-3beta inactivation was observed in human tumor tissues, indicating that GSK-3beta inactivation may account for Cdc25A overproduction in a subset of human tumors.
Relation:	CANCER CELL 13(-):36-47
Appears in Collections:	[Department of Biotechnology] Journal Article

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