PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2.
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Yang S, Kuo C, Bisi JE, Kim MK
PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2.
Nat Cell Biol. 2002 Nov;4(11):865-70.
- PubMed ID
- 12402044 [ View in PubMed]
- 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.