磷酸化
激酶
生物
肌醇
程序性细胞死亡
细胞生物学
细胞凋亡
丝氨酸
丝氨酸苏氨酸激酶
信号转导
生物化学
蛋白激酶A
受体
作者
Feng Rao,Ji-Young Cha,Jing Xu,Risheng Xu,M. Scott Vandiver,Richa Tyagi,Robert Tokhunts,Michael A. Koldobskiy,Cheng Fu,Roxanne K. Barrow,Mingxuan Wu,Dorothea Fiedler,James C. Barrow,Solomon H. Snyder
出处
期刊:Molecular Cell
[Elsevier]
日期:2014-04-01
卷期号:54 (1): 119-132
被引量:103
标识
DOI:10.1016/j.molcel.2014.02.020
摘要
The apoptotic actions of p53 require its phosphorylation by a family of phosphoinositide-3-kinase-related-kinases (PIKKs), which include DNA-PKcs and ATM. These kinases are stabilized by the TTT (Tel2, Tti1, Tti2) cochaperone family, whose actions are mediated by CK2 phosphorylation. The inositol pyrophosphates, such as 5-diphosphoinositol pentakisphosphate (IP7), are generated by a family of inositol hexakisphosphate kinases (IP6Ks), of which IP6K2 has been implicated in p53-associated cell death. In the present study we report an apoptotic signaling cascade linking CK2, TTT, the PIKKs, and p53. We demonstrate that IP7, formed by IP6K2, binds CK2 to enhance its phosphorylation of the TTT complex, thereby stabilizing DNA-PKcs and ATM. This process stimulates p53 phosphorylation at serine 15 to activate the cell death program in human cancer cells and in murine B cells.
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