Direct interaction of c-Myc with Smad2 and Smad3 to inhibit TGF-β-mediated induction of the CDK inhibitor p15Ink4B

被引：183

作者：

Feng, XH ^{[1
]}

Liang, YY

Liang, M

Zhai, WG

Lin, X

机构：

[1] Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA

[2] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[3] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

来源：

MOLECULAR CELL | 2002年 / 9卷 / 01期

关键词：

D O I：

10.1016/S1097-2765(01)00430-0

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：

The c-Myc oncogene has been implicated in the genesis of diverse human tumors. Ectopic expression of the c-Myc gene in cultured epithelial cells causes resistance to the antiproliferative effects of TGF-beta. However, little is known about the precise mechanisms of c-Myc-mediated TGF-beta resistance. In this study, we reveal that c-Myc physically interacts with Smad2 and Smad3, two specific signal transducers involved in TGF-beta signaling. Through its direct interaction with Smads, c-Myc binds to the Sp1-Smad complex on the promoter of the p15(Ink4B) gene, thereby inhibiting the TGF-beta-induced transcriptional activity of Sp1 and Smad/Sp1-dependent transcription of the p15(Ink4B) gene. These results suggest that oncogenic c-Myc promotes cell growth and cancer development partly by inhibiting the growth inhibitory functions of Smads.

引用

页码：133 / 143

页数：11

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