期刊
ONCOGENE
卷 28, 期 5, 页码 698-708出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2008.420
关键词
HIPK2; PML; phosphorylation; cell death
资金
- Deutsche Forschungsgemeinschaft [SCHM 1417/4-1, SCHM 1417/5-1, SFB 547]
- ECCPS-Excellence Cluster Cardio-Pulmonary System
- Swiss Cancer League [OCS 01667-02-2005]
The promyelocytic leukemia (PML) tumor suppressor protein, a central regulator of cell proliferation and apoptosis, is frequently fused to the retinoic acid receptor-alpha (RAR alpha) in acute PML. Here we show the interaction of PML with another tumor suppressor protein, the serine/threonine kinase homeodomain-interacting protein kinase (HIPK2). In response to DNA damage, HIPK2 phosphorylates PML at serines 8 and 38. Although HIPK2-mediated phosphorylation of PML occurs early during the DNA damage response, the oncogenic PML-RAR alpha fusion protein is phosphorylated with significantly delayed kinetics. DNA damage or HIPK2 expression leads to the stabilization of PML and PML-RARa proteins. The N-terminal phosphorylation sites contribute to the DNA damage-induced PML SUMOylation and are required for the ability of PML to cooperate with HIPK2 for the induction of cell death.
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