| Literature DB >> 19203584 |
Mingan Shi1, Carolyn J Vivian, Kyung-Jong Lee, Chunmin Ge, Keiko Morotomi-Yano, Claudia Manzl, Florian Bock, Shigeo Sato, Chieri Tomomori-Sato, Ruihong Zhu, Jeffrey S Haug, Selene K Swanson, Michael P Washburn, David J Chen, Benjamin P C Chen, Andreas Villunger, Laurence Florens, Chunying Du.
Abstract
Caspase-2 is unique among all the mammalian caspases in that it is the only caspase that is present constitutively in the cell nucleus, in addition to other cellular compartments. However, the functional significance of this nuclear localization is unknown. Here we show that DNA damage induced by gamma-radiation triggers the phosphorylation of nuclear caspase-2 at the S122 site within its prodomain, leading to its cleavage and activation. This phosphorylation is carried out by the nuclear serine/threonine protein kinase DNA-PKcs and promoted by the p53-inducible death-domain-containing protein PIDD within a large nuclear protein complex consisting of DNA-PKcs, PIDD, and caspase-2, which we have named the DNA-PKcs-PIDDosome. This phosphorylation and the catalytic activity of caspase-2 are involved in the maintenance of a G2/M DNA damage checkpoint and DNA repair mediated by the nonhomologous end-joining (NHEJ) pathway. The DNA-PKcs-PIDDosome thus represents a protein complex that impacts mammalian G2/M DNA damage checkpoint and NHEJ.Entities:
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Year: 2009 PMID： 19203584 PMCID： PMC5647584 DOI： 10.1016/j.cell.2008.12.021
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582