PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2 - PubMed (original) (raw)
PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2
Shutong Yang et al. Nat Cell Biol. 2002 Nov.
Abstract
The promyelocytic leukaemia (PML) gene is translocated in most acute promyelocytic leukaemias and encodes a tumour suppressor protein. PML is involved in multiple apoptotic pathways and is thought to be pivotal in gamma irradiation-induced apoptosis. The DNA damage checkpoint kinase hCds1/Chk2 is necessary for p53-dependent apoptosis after gamma irradiation. In addition, gamma irradiation-induced apoptosis also occurs through p53-independent mechanisms, although the molecular mechanism remains largely unknown. Here, we report that hCds1/Chk2 mediates gamma irradiation-induced apoptosis in a p53-independent manner through an ataxia telangiectasia-mutated (ATM)-hCds1/Chk2-PML pathway. Our results provide the first evidence of a functional relationship between PML and a checkpoint kinase in gamma irradiation-induced apoptosis.
Comment in
- Chk2 leaves the PML depot.
Venere M, Mochan TA, Halazonetis TD. Venere M, et al. Nat Cell Biol. 2002 Nov;4(11):E255-6. doi: 10.1038/ncb1102-e255. Nat Cell Biol. 2002. PMID: 12415282 No abstract available.
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