Phosphorylation of HDM2 by Akt
Phosphorylation of HDM2 by Akt
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DOI：
10.1038/sj.onc.1205276
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发表时间：
2002-03-21
期刊：
影响因子：
8
通讯作者：
Vousden, KH
中科院分区：
文献类型：
--
作者：
Ashcroft, M;Ludwig, RL;Vousden, KH
Hdm2蛋白是肿瘤抑制基因P53的关键调节因子。Hdm2的功能调控对于正常的细胞增殖和应激反应至关重要，而且越来越明显的是，Hdm2的多重修饰可以调节其在细胞内的功能。在这项研究中，我们发现Hdm2与丝氨酸苏氨酸激酶Akt相关，以响应生长因子对人类原代细胞的刺激。这种关联与Akt的磷酸化(位于Ser473)是同步的，并导致Hdm2的表达增加和核定位增强。然而，对在丝氨酸166和186上共同的Akt识别位点突变的Hdm2蛋白的分析表明，这些残基的修饰不足以增加该蛋白的表达，该蛋白可被PI3激酶抑制剂LY294002阻断。胰多肽和突变分析显示，除了两个共识位点外，Hdm2中还存在Akt磷酸化位点。
The HDM2 protein is a key regulator of the tumour suppressor, p53. Control of HDM2 function is critical for normal cell proliferation and stress responses, and it is becoming evident that multiple modifications of HDM2 can regulate its function within cells. In this study we show that HDM2 associated with the serinethreonine kinase, Akt, in response to growth factor stimulation of human primary cells. This association was concurrent with phosphorylation of Akt (at Ser 473), and resulted in elevated expression of HDM2 and enhanced nuclear localization. However, analysis of HDM2 proteins mutated at the consensus Akt recognition sites at serines 166 and 186 indicated that modification at these residues was not sufficient for the increased expression of the protein, which was blocked by the PI3 kinase inhibitor LY294002. Tryptic peptide and mutational analyses revealed evidence for an Akt phosphorylation site in HDM2 additional to the two consensus sites.