Journal article
PIDDosome-independent tumor suppression by Caspase-2
C Manzl, L Peintner, G Krumschnabel, F Bock, V Labi, M Drach, A Newbold, R Johnstone, A Villunger
Cell Death and Differentiation | Published : 2012
DOI: 10.1038/cdd.2012.54
Abstract
The PIDDosome, a multiprotein complex constituted of the p53-induced protein with a death domain (PIDD), receptor-interacting protein (RIP)-associated ICH-1/CED-3 homologous protein with a death domain (RAIDD) and pro-Caspase-2 has been defined as an activating platform for this apoptosis-related protease. PIDD has been implicated in p53-mediated cell death in response to DNA damage but also in DNA repair and nuclear factor kappa-light-chain enhancer (NF-B) activation upon genotoxic stress, together with RIP-1 kinase and Nemo/IKKγ. As all these cellular responses are critical for tumor suppression and deregulated expression of individual PIDDosome components has been noted in human cancer, w..
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Awarded by Cancer Council Victoria
Funding Acknowledgements
We thank K Rossi and B Rieder for animal husbandry; C Soratroi, R Pfeilschifter, I Gaggl and I Brosch for excellent technical assistance; P Lukas and his team (LINAC1-4) for enabling irradiation of mice (Center of Nuclear Medicine and Radiotherapy, University Medical Center of Innsbruck); G Bock for cell sorting; G Baier and N Herman-Kleiter for help with Bioplex analysis; D Vaux for Casp2<SUP>-/-</SUP> and M Serrano for p53<SUP>-/-</SUP> mice. This study was funded by the Austrian Science Fund (FWF; Y212-B12; SFB021), AICR project 06-440 to AV and the FP06 RTN 'ApopTrain' to AV and FB as well as the Daniel Swarovski Fond (DSF) and the Tyrolean Science Fund (TWF) to CM and the Austrian Krebshilfe-Tirol (CM and GK). RWJ is a Principal Research Fellow of the National Health and Medical Research Council of Australia (NHMRC) and supported by NHMRC Program and Project Grants, the Susan G Komen Breast Cancer Foundation, the Prostate Cancer Foundation of Australia, Cancer Council Victoria, The Leukemia Foundation of Australia, Victorian Breast Cancer Research Consortium, Victorian Cancer Agency and the Australian Rotary Health Foundation.