HDM2 phosphorylation by MAPKAP kinase 2.
HDM2 phosphorylation by MAPKAP kinase 2.
复制标题
MAPKAP 激酶 2 使 HDM2 磷酸化。
DOI：
10.1038/sj.onc.1208389
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发表时间：
2005
期刊：
影响因子：
8
通讯作者：
Vousden,KarenH
中科院分区：
文献类型：
--
作者：
Weber,HansOliver;Ludwig,RobertL;Morrison,Deborah;Kotlyarov,Alexey;Gaestel,Matthias;Vousden,KarenH
P53的稳定性由Hdm2调节，Hdm2是一种环状结构域蛋白，作为E3连接酶泛化P53并针对其降解。AKT使Hdm2在丝氨酸166上的磷酸化可以增强Hdm2的活性，并促进P53的降解。在此，我们发现MAPKAP激酶2(MK2)在体外可以使Hdm2在丝氨酸157和166上磷酸化。在体内，用激活MK2的茴香霉素处理细胞，也会导致Hdm2在丝氨酸157和166上的磷酸化。Hdm2的MK2磷酸化位点突变为天冬氨酸使Hdm2在P53的降解中略微更活跃，而MK2缺失的小鼠细胞显示MDM2磷酸化降低和P53蛋白水平升高。总之，我们的结果表明，MK2可能会抑制P53反应的范围和持续时间。
p53 stability is regulated by HDM2, a RING domain protein that acts as an E3 ligase to ubiquitinate p53 and target its degradation. Phosphorylation of HDM2 on serine 166 by AKT has been shown to enhance HDM2 activity and promote the degradation of p53. Here, we show that MAPKAP kinase 2 (MK2) can phosphorylate HDM2 on serine 157 and 166 in vitro. Treatment of cells with anisomycin, which activates MK2, also results in phosphorylation of HDM2 on serine 157 and 166 in vivo. Mutation of the MK2 phosphorylation sites in HDM2 to aspartic acid renders HDM2 slightly more active in the degradation of p53, and mouse cells deficient for MK2 show reduced Mdm2 phosphorylation and elevated levels of p53 protein. Together, our results suggest that MK2 may act to dampen the extent and duration of the p53 response.