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 γ irradiation-induced apoptosis. The DNA damage checkpoint kinase hCds1/Chk2 is necessary for p53-dependent apoptosis after γ irradiation. In addition, γ irradiation-induced apoptosis also occurs through p53-independent mechanisms, although the molecular mechanism remains largely unknown. Here, we report that hCds1/Chk2 mediates γ 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 γ irradiation-induced apoptosis.
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Acknowledgements
We thank M. Alcalay for the PML vector; J. H. Chung for the V5–hCds1/Chk2(WT, KD) constructs and anti-hCds1/Chk2 antibodies; Y. Shiloh for the AT cells; Y. Xu and C. Combs for help with confocal microscopy; J. P. Cogswell and C. E. Brown for help with recombinant adenovirus production.
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Yang, S., Kuo, C., Bisi, J. et al. PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2. Nat Cell Biol 4, 865–870 (2002). https://doi.org/10.1038/ncb869
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DOI: https://doi.org/10.1038/ncb869
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