SMG-1 suppresses CDK2 and tumor growth by regulating both the p53 and Cdc25A signaling pathways

被引：35

作者：

Gubanova, Evgenia ^{[1
,2
]}

Issaeva, Natalia ^{[3
,4
]}

Gokturk, Camilla ^{[2
]}

Djureinovic, Tatjana ^{[1
]}

Helleday, Thomas ^{[2
]}

机构：

[1] Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden

[2] Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden

[3] Yale Univ, Dept Surg, New Haven, CT USA

[4] Yale Univ, Ctr Canc, New Haven, CT USA

来源：

CELL CYCLE | 2013年 / 12卷 / 24期

基金：

瑞典研究理事会; 欧洲研究理事会;

关键词：

Cdc25A; CDK2; cell cycle; G(1)/S checkpoint; p53; SMG-1; tumorigenesis; tumor suppressor; RNA SURVEILLANCE PROTEIN; HUMAN BREAST-CANCER; DNA-DAMAGE; MESSENGER-RNA; S-PHASE; GENOMIC INSTABILITY; IONIZING-RADIATION; OXIDATIVE STRESS; BETA-TRCP; DEGRADATION;

D O I：

10.4161/cc.26660

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The DNA damage response is coordinated by phosphatidylinositol 3-kinase-related kinases, ATM, ATR, and DNA-PK. SMG-1 is the least studied stress-responsive member of this family. Here, we show that SMG-1 regulates the G(1)/S checkpoint through both a p53-dependent, and a p53-independent pathway. We identify Cdc25A as a new SMG-1 substrate, and show that cells depleted of SMG-1 exhibit prolonged Cdc25A stability, failing to inactivate CDK2 in response to radiation. Given an increased tumor growth following depletion of SMG-1, our data demonstrate a novel role for SMG-1 in regulating Cdc25A and suppressing oncogenic CDK2 driven proliferation, confirming SMG-1 as a tumor suppressor.

引用

页码：3770 / 3780

页数：11

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