GSK-3β-dependent destabilization of cyclin D1 mediates replicational stress-induced arrest of cell cycle

被引：14

作者：

Mukherji, Atish ^{[1
]}

Janbandbu, Vaibhao C. ^{[1
]}

Kumar, Vijay ^{[1
]}

机构：

[1] Int Ctr Genet Engn & Biotechnol, Virol Grp, New Delhi 110067, India

来源：

FEBS LETTERS | 2008年 / 582卷 / 07期

关键词：

cell cycle; cyclin D1; genotoxic stress; GSK-3; beta; hydroxyurea; PKB/Akt;

D O I：

10.1016/j.febslet.2008.02.068

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Chemotherapeutic agents are well known to induce growth arrest of cancerous cells by inducing DNA damage/replicational stress and engaging cellular apoptotic machinery. Our studies on hydroxyurea (HU) recognized cyclin D1 destabilization as the initiator of growth arrest at G(1)/S-phase independent of other cell cycle regulators. Cyclin D1 degradation was associated with its phosphorylation at Thr286 by glycogen synthase kinase-3 beta and inactivation of Akt kinase. Overexpression of the cyclin D-1(T286A) mutant, or constitutively active Akt, conferred stability to cyclin D1 and helped bypass cell cycle arrest. Thus, growth arrest by HU seems to involve destabilization of cyclin D1 in addition to its well-established role as ribonucleotide reductase inhibitor. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：1111 / 1116

页数：6

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