Autophagy mediates the mitotic senescence transition

被引：816

作者：

Young, Andrew R. J. ^{[1
]}

Narita, Masako ^{[1
]}

Ferreira, Manuela ^{[1
,2
]}

Kirschner, Kristina ^{[1
]}

Sadaie, Mahito ^{[1
]}

Darot, Jeremy F. J. ^{[1
,3
]}

Tavare, Simon ^{[1
]}

Arakawa, Satoko ^{[4
]}

Shimizu, Shigeomi ^{[4
]}

Watt, Fiona M. ^{[1
]}

Narita, Masashi ^{[1
]}

机构：

[1] Li Ka Shing Ctr, Cambridge Res Inst, Cambridge CB2 0RE, England

[2] Univ Coimbra, Ctr Neurosci & Cell Biol, P-3004517 Coimbra, Portugal

[3] Wellcome Trust Genome, EMBL EBI, Cambridge CB10 1SD, England

[4] Tokyo Med & Dent Univ, Dept Pathol & Cell Biol, Med Res Inst, Bunkyo Ku, Tokyo 1138510, Japan

来源：

GENES & DEVELOPMENT | 2009年 / 23卷 / 07期

关键词：

Senescence; autophagy; oncogene; ONCOGENE-INDUCED SENESCENCE; CELLULAR SENESCENCE; TUMOR-SUPPRESSOR; TUMORIGENESIS; PROTEIN; CANCER; DAMAGE; STARVATION; CELLS; DEFICIENT;

D O I：

10.1101/gad.519709

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

As a stress response, senescence is a dynamic process involving multiple effector mechanisms whose combination determines the phenotypic quality. Here we identify autophagy as a new effector mechanism of senescence. Autophagy is activated during senescence and its activation is correlated with negative feedback in the PI3K-mammalian target of rapamycin (mTOR) pathway. A subset of autophagy-related genes are up-regulated during senescence: Overexpression of one of those genes, ULK3, induces autophagy and senescence. Furthermore, inhibition of autophagy delays the senescence phenotype, including senescence-associated secretion. Our data suggest that autophagy, and its consequent protein turnover, mediate the acquisition of the senescence phenotype.

引用

页码：798 / 803

页数：6

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