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Genes & development v.31 no.1, 2017년, pp.34 - 45   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

The PIDDosome activates p53 in response to supernumerary centrosomes

Fava, Luca L. (Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria ); Schuler, Fabian (Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria ); Sladky, Valentina (Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria ); Haschka, Manuel D. (Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria ); Soratroi, Claudia (Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria ); Eiterer, Lisa (Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria ); Demetz, Egon (Department of Internal Medicine VI, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, 6020 Innsbruck, Austria ); Weiss, Guenter (Department of Internal Medicine VI, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, 6020 Innsbruck, Austria ); Geley, Stephan (Division of Molecular Pathophysiolog ); Nigg, Erich A. ( ); Villunger, Andreas ( );
  • 초록  

    In this study, Fava et al. show that an increase in the number of mature centrosomes (the main microtubule-organizing centers in animal cells), 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. 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 PIDDosome acts as a first barrier, engaging p53 to halt the proliferation of cells carrying more than one mature centrosome to maintain genome integrity.


  • 주제어

    cell division .   centrosome .   cytokinesis failure .   p53.  

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