Regulation of autophagy by cytoplasmic p53

被引：916

作者：

Tasdemir, Ezgi ^{[1
,2
,3
]}

Maiuri, M. Chiara ^{[1
,2
,4
,5
]}

Galluzzi, Lorenzo ^{[1
,2
,3
]}

Vitale, Ilio ^{[1
,2
,3
]}

Djavaheri-Mergny, Mojgan ^{[6
]}

D'Amelio, Marcello ^{[9
,10
]}

Criollo, Alfredo ^{[1
,2
,3
]}

Morselli, Eugenia ^{[1
,2
,3
]}

Zhu, Changlian ^{[17
]}

Harper, Francis ^{[16
]}

Nannmark, Ulf ^{[15
]}

Samara, Chrysanthi ^{[14
]}

Pinton, Paolo ^{[13
]}

Vicencio, Jose Miguel ^{[1
,2
,3
]}

Carnuccio, Rosa ^{[4
,5
]}

Moll, Ute M. ^{[12
]}

Madeo, Frank ^{[11
]}

Paterlini-Brechot, Patrizia ^{[8
]}

Rizzuto, Rosario ^{[13
]}

Szabadkai, Gyorgy ^{[7
,8
]}

Pierron, Gerard ^{[16
]}

Blomgren, Klas ^{[17
]}

Tavernarakis, Nektarios ^{[14
]}

Codogno, Patrice ^{[6
]}

Cecconi, Francesco ^{[9
,10
]}

Kroemer, Guido ^{[1
,2
,3
]}

机构：

[1] Inst Gustave Roussy, F-94805 Villejuif, France

[2] INSERM, U848, F-94805 Villejuif, France

[3] Univ Paris 11, F-94805 Villejuif, France

[4] Univ Naples Federico II, Sch Biotechnol Sci, I-80131 Naples, Italy

[5] Univ Naples Federico II, Dept Expt Pharmacol, I-80131 Naples, Italy

[6] Univ Paris 11, Fac Pharm, INSERM, U756, F-92290 Chatenay Malabry, France

[7] UCL, Dept Physiol, London WC1E 6BT, England

[8] Univ Paris 05, Hop Necker Enfants Malad, Fac Med, INSERM U807, F-75015 Paris, France

[9] Univ Roma Tor Vergata, Dept Biol, Dulbecco Telethon Inst, I-00133 Rome, Italy

[10] IRCCS, Fondaz Santa Lucia, I-00133 Rome, Italy

[11] Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria

[12] SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA

[13] Univ Ferrara, ICSI, Dept Expt & Diagnost Med, Sect Gen Pathol, I-44100 Ferrara, Italy

[14] Fdn Res & Technol Hellas, Inst Mol Biol & Biotechnol, Iraklion, Crete, Greece

[15] Gothenburg Univ, Inst Biomed, Dept Med Biochem & Cell Biol, S-41124 Gothenburg, Sweden

[16] Inst Andre Lwoff, CNRS, FRE 2937, F-94801 Villejuif, France

[17] Gothenburg Univ, Queen Silvia Childrens Hosp, Dept Pediat Oncol, Inst Neurosci & Physiol,Ctr Brain Repair & Rehabi, Gothenburg, Sweden

来源：

NATURE CELL BIOLOGY | 2008年 / 10卷 / 06期

关键词：

D O I：

10.1038/ncb1730

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Multiple cellular stressors, including activation of the tumour suppressor p53, can stimulate autophagy. Here we show that knockout, knockdown or pharmacological inhibition of p53 can induce autophagy in human, mouse and nematode cells. Enhanced autophagy improved the survival of p53-deficient cancer cells under conditions of hypoxia and nutrient depletion, allowing them to maintain high ATP levels. Inhibition of p53 led to autophagy in enucleated cells, and cytoplasmic, not nuclear, p53 was able to repress the enhanced autophagy of p53(-/-)cells. Many different inducers of autophagy (for example, starvation, rapamycin and toxins affecting the endoplasmic reticulum) stimulated proteasome-mediated degradation of p53 through a pathway relying on the E3 ubiquitin ligase HDM2. Inhibition of p53 degradation prevented the activation of autophagy in several cell lines, in response to several distinct stimuli. These results provide evidence of a key signalling pathway that links autophagy to the cancer-associated dysregulation of p53.

引用

页码：676 / 687

页数：12

共 50 条

[1] Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma [J].

Amaravadi, Ravi K. ;

Yu, Duonan ;

Lum, Julian J. ;

Bui, Thi ;

Christophorou, Maria A. ;

Evan, Gerard I. ;

Thomas-Tikhonenko, Andrei ;

Thompson, Craig B. .

JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (02) :326-336

[2] CHROMOSOME-17 DELETIONS AND P53 GENE-MUTATIONS IN COLORECTAL CARCINOMAS [J].

BAKER, SJ ;

FEARON, ER ;

NIGRO, JM ;

HAMILTON, SR ;

PREISINGER, AC ;

JESSUP, JM ;

VANTUINEN, P ;

LEDBETTER, DH ;

BARKER, DF ;

NAKAMURA, Y ;

WHITE, R ;

VOGELSTEIN, B .

SCIENCE, 1989, 244 (4901) :217-221

[3] Inhibition of macroautophagy triggers apoptosis [J].

Boya, P ;

González-Polo, RA ;

Casares, N ;

Perfettini, JL ;

Dessen, P ;

Larochette, N ;

Métivier, D ;

Meley, D ;

Souquere, S ;

Yoshimori, T ;

Pierron, G ;

Codogno, P ;

Kroemer, G .

MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (03) :1025-1040

[4] Hypoxia signalling controls metabolic demand [J].

Brahimi-Horn, M. Christiane ;

Chiche, Johanna ;

Pouyssegur, Jacques .

CURRENT OPINION IN CELL BIOLOGY, 2007, 19 (02) :223-229

[5] Disruption of p53 in human cancer cells alters the responses to therapeutic agents [J].

Bunz, F ;

Hwang, PM ;

Torrance, C ;

Waldman, T ;

Zhang, YG ;

Dillehay, L ;

Williams, J ;

Lengauer, C ;

Kinzler, KW ;

Vogelstein, B .

JOURNAL OF CLINICAL INVESTIGATION, 1999, 104 (03) :263-269

[6] Pharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of transcription [J].

Chipuk, JE ;

Maurer, U ;

Green, DR ;

Schuler, M .

CANCER CELL, 2003, 4 (05) :371-381

[7] Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis [J].

Chipuk, JE ;

Kuwana, T ;

Bouchier-Hayes, L ;

Droin, NM ;

Newmeyer, D ;

Schuler, M ;

Green, DR .

SCIENCE, 2004, 303 (5660) :1010-1014

[8] DRAM, a p53-induced modulator of autophagy, is critical for apoptosis [J].

Crighton, Diane ;

Wilkinson, Simon ;

O'Prey, Jim ;

Syed, Nelofer ;

Smith, Paul ;

Harrison, Paul R. ;

Gasco, Milena ;

Garrone, Ornella ;

Crook, Tim ;

Ryan, Kevin M. .

CELL, 2006, 126 (01) :121-134

[9] Regulation of autophagy by the inositol trisphosphate receptor [J].

Criollo, A. ;

Maiuri, M. C. ;

Tasdemir, E. ;

Vitale, I. ;

Fiebig, A. A. ;

Andrews, D. ;

Molgo, J. ;

Diaz, J. ;

Lavandero, S. ;

Harper, F. ;

Pierron, G. ;

di Stefano, D. ;

Rizzuto, R. ;

Szabadkai, G. ;

Kroemer, G. .

CELL DEATH AND DIFFERENTIATION, 2007, 14 (05) :1029-1039

[10] Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis [J].

Degenhardt, Kurt ;

Mathew, Robin ;

Beaudoin, Brian ;

Bray, Kevin ;

Anderson, Diana ;

Chen, Guanghua ;

Mukherjee, Chandreyee ;

Shi, Yufang ;

Gelinas, Celine ;

Fan, Yongjun ;

Nelson, Deirdre A. ;

Jin, Shengkan ;

White, Eileen .

CANCER CELL, 2006, 10 (01) :51-64

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