PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2 NATURE CELL BIOLOGY Yang, S. T., Kuo, C., Bisi, J. E., Kim, M. K. 2002; 4 (11): 865-870

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.

View details for DOI 10.1038/ncb869

View details for Web of Science ID 000179137700015

View details for PubMedID 12402044