TGF-β inhibits p70 S6 kinase via protein phosphatase 2A to induce G1 arrest

被引：185

作者：

Petritsch, C

Beug, H

Balmain, A

Oft, M ^{[1
]}

机构：

[1] Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA

[2] IMP, Res Inst Mol Pathol, A-1030 Vienna, Austria

[3] Onyx Pharmaceut, Richmond, CA 94801 USA

来源：

GENES & DEVELOPMENT | 2000年 / 14卷 / 24期

关键词：

TGF-beta p70(s6k); PP2A; G(1) arrest; cell cycle;

D O I：

10.1101/gad.854200

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

On TGF-beta binding, the TGF-beta receptor directly phosphorylates and activates the transcription factors Smad2/3, leading to G(1) arrest. Here, we present evidence for a second, parallel, TGF-beta -dependent pathway for cell cycle arrest, achieved via inhibition of p70(s6k). TGF-beta induces association of its receptor with protein phosphatase-2A (PP2A)-B alpha. Concomitantly, three PP2A-subunits, B alpha, A beta, and C alpha, associate with p70(s6k), leading to its dephosphorylation and inactivation. Although either pathway is sufficient to induce G(1) arrest, abrogation of both, the inhibition of p70(s6k), and transcription through Smad proteins is required for release of epithelial cells from TGF-beta -induced G(1) arrest. TGF-beta thereby modulates the translational and posttranscriptional control of cell cycle progression.

引用

页码：3093 / 3101

页数：9

共 36 条

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BALLOU LM, 1988, J BIOL CHEM, V263, P1188

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