The PIDDosome activates p53 in response to supernumerary centrosomes

被引：161

作者：

Fava, Luca L. ^{[1
]}

Schuler, Fabian ^{[1
]}

Sladky, Valentina ^{[1
]}

Haschka, Manuel D. ^{[1
]}

Soratroi, Claudia ^{[1
]}

Eiterer, Lisa ^{[1
]}

Demetz, Egon ^{[2
]}

Weiss, Guenter ^{[2
]}

Geley, Stephan ^{[3
]}

Nigg, Erich A. ^{[4
]}

Villunger, Andreas ^{[1
,5
]}

机构：

[1] Med Univ Innsbruck, Divis Dev Immunol, Bioctr, A-6020 Innsbruck, Austria

[2] Med Univ Innsbruck, Dept Internal Med 6, Infect Dis Immunol Rheumatol Pneumol, A-6020 Innsbruck, Austria

[3] Med Univ Innsbruck, Div Mol Pathophysiol, Bioctr, A-6020 Innsbruck, Austria

[4] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland

[5] Tyrolean Canc Res Inst, A-6020 Innsbruck, Austria

来源：

GENES & DEVELOPMENT | 2017年 / 31卷 / 01期

基金：

奥地利科学基金会; 瑞士国家科学基金会;

关键词：

cell division; centrosome; cytokinesis failure; p53; DNA-DAMAGE; CHROMOSOMAL INSTABILITY; P53-INDUCED PROTEIN; MITOTIC CATASTROPHE; CASPASE-2; CANCER; CELLS; DEATH; DUPLICATION; SUPPRESSION;

D O I：

10.1101/gad.289728.116

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Centrosomes, the main microtubule-organizing centers in animal cells, are replicated exactly once during the cell division cycle to form the poles of the mitotic spindle. Supernumerary centrosomes can lead to aberrant cell division and have been causally linked to chromosomal instability and cancer. Here, we report that an increase in the number of mature centrosomes, generated by disrupting cytokinesis or forcing centrosome overduplication, triggers the activation of the PIDDosome multiprotein complex, leading to Caspase-2-mediated MDM2 cleavage, p53 stabilization, and p21-dependent cell cycle arrest. This pathway also restrains the extent of developmentally scheduled polyploidization by regulating p53 levels in hepatocytes during liver organogenesis. Taken together, the PIDD osome acts as a first barrier, engaging p53 to halt the proliferation of cells carrying more than one mature centrosome to maintain genome integrity.

引用

页码：34 / 45

页数：12

共 58 条

[1] A positive feedback loop between the p53 and Lats2 tumor suppressors prevents tetraploidization [J].

Aylon, Yael ;

Michael, Dan ;

Shmueli, Ayelet ;

Yabuta, Norikazu ;

Nojima, Hiroshi ;

Oren, Moshe .

GENES & DEVELOPMENT, 2006, 20 (19) :2687-2700

[2] The biochemical mechanism of caspase-2 activation [J].

Baliga, BC ;

Read, SH ;

Kumar, S .

CELL DEATH AND DIFFERENTIATION, 2004, 11 (11) :1234-1241

[3] P53-induced protein with a death domain (PIDD): master of puppets? [J].

Bock, F. J. ;

Peintner, L. ;

Tanzer, M. ;

Manzl, C. ;

Villunger, A. .

ONCOGENE, 2012, 31 (45) :4733-4739

[4] Mitotic catastrophe constitutes a special case of apoptosis whose suppression entails aneuploidy [J].

Castedo, M ;

Perfettini, JL ;

Roumier, T ;

Valent, A ;

Raslova, H ;

Yakushijin, K ;

Horne, D ;

Feunteun, J ;

Lenoir, G ;

Medema, R ;

Vainchenker, W ;

Kroemer, G .

ONCOGENE, 2004, 23 (25) :4362-4370

[5] Over-expression of Plk4 induces centrosome amplification, loss of primary cilia and associated tissue hyperplasia in the mouse [J].

Coelho, Paula A. ;

Bury, Leah ;

Shahbazi, Marta N. ;

Liakath-Ali, Kifayathullah ;

Tate, Peri H. ;

Wormald, Sam ;

Hindley, Christopher J. ;

Huch, Meritxell ;

Archer, Joy ;

Skarnes, William C. ;

Zernicka-Goetz, Magdalena ;

Glover, David M. .

OPEN BIOLOGY, 2015, 5 (12)

[6] Centrosome function and assembly in animal cells [J].

Conduit, Paul T. ;

Wainman, Alan ;

Raff, Jordan W. .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2015, 16 (10) :611-624

[7] DNA breaks and chromosome pulverization from errors in mitosis [J].

Crasta, Karen ;

Ganem, Neil J. ;

Dagher, Regina ;

Lantermann, Alexandra B. ;

Ivanova, Elena V. ;

Pan, Yunfeng ;

Nezi, Luigi ;

Protopopov, Alexei ;

Chowdhury, Dipanjan ;

Pellman, David .

NATURE, 2012, 482 (7383) :53-U70

[8] p53-induced protein with a death domain (PIDD) isoforms differentially activate nuclear factor-kappaB and caspase-2 in response to genotoxic stress [J].

Cuenin, S. ;

Tinel, A. ;

Janssens, S. ;

Tschopp, J. .

ONCOGENE, 2008, 27 (03) :387-396

[9] The Causes and Consequences of Polyploidy in Normal Development and Cancer [J].

Davoli, Teresa ;

de Lange, Titia .

ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 27, 2011, 27 :585-610

[10] Spatial and temporal diversity in genomic instability processes defines lung cancer evolution [J].

de Bruin, Elza C. ;

McGranahan, Nicholas ;

Mitter, Richard ;

Salm, Max ;

Wedge, David C. ;

Yates, Lucy ;

Jamal-Hanjani, Mariam ;

Shafi, Seema ;

Murugaesu, Nirupa ;

Rowan, Andrew J. ;

Groenroos, Eva ;

Muhammad, Madiha A. ;

Horswell, Stuart ;

Gerlinger, Marco ;

Varela, Ignacio ;

Jones, David ;

Marshall, John ;

Voet, Thierry ;

Van Loo, Peter ;

Rassl, Doris M. ;

Rintoul, Robert C. ;

Janes, Sam M. ;

Lee, Siow-Ming ;

Forster, Martin ;

Ahmad, Tanya ;

Lawrence, David ;

Falzon, Mary ;

Capitanio, Arrigo ;

Harkins, Timothy T. ;

Lee, Clarence C. ;

Tom, Warren ;

Teefe, Enock ;

Chen, Shann-Ching ;

Begum, Sharmin ;

Rabinowitz, Adam ;

Phillimore, Benjamin ;

Spencer-Dene, Bradley ;

Stamp, Gordon ;

Szallasi, Zoltan ;

Matthews, Nik ;

Stewart, Aengus ;

Campbell, Peter ;

Swanton, Charles .

SCIENCE, 2014, 346 (6206) :251-256

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