Genetic interrogation of replicative senescence uncovers a dual role for USP28 in coordinating the p53 and GATA4 branches of the senescence program

被引：27

作者：

Mazzucco, Anna E. ^{[1
]}

Smogorzewska, Agata ^{[1
,2
,3
]}

Kang, Chanhee ^{[1
,4
]}

Luo, Ji ^{[1
,5
]}

Schlabach, Michael R. ^{[1
,6
]}

Xu, Qikai ^{[1
]}

Patel, Rupesh ^{[1
]}

Elledge, Stephen J. ^{[1
]}

机构：

[1] Harvard Med Sch, Howard Hughes Med Inst, Brigham & Womens Hosp, Dept Genet,Div Genet, Boston, MA 02115 USA

[2] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[3] Rockefeller Univ, New York, NY 10065 USA

[4] Seoul Natl Univ, Sch Biol Sci, Seoul 08826, South Korea

[5] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA

[6] KSQ Pharmaceut, Cambridge, MA 02139 USA

来源：

GENES & DEVELOPMENT | 2017年 / 31卷 / 19期

基金：

美国国家卫生研究院;

关键词：

GATA4; senescence; USP28; ONCOGENE-INDUCED SENESCENCE; DNA-DAMAGE RESPONSE; CELLULAR SENESCENCE; CANCER; CELLS; PATHWAYS; NETWORK; GENOME;

D O I：

10.1101/gad.304857.117

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Senescence is a terminal differentiation program that halts the growth of damaged cells and must be circumvented for cancer to arise. Here we describe a panel of genetic screens to identify genes required for replicative senescence. We uncover a role in senescence for the potent tumor suppressor and ATM substrate USP28. USP28 controls activation of both the TP53 branch and the GATA4/NFkB branch that controls the senescence-associated secretory phenotype (SASP). These results suggest a role for ubiquitination in senescence and imply a common node downstream from ATM that links the TP53 and GATA4 branches of the senescence response.

引用

页码：1933 / 1938

页数：6