Modification of p53 with O-linked N-acetylglucosamine regulates p53 activity and stability
Modification of p53 with O-linked N-acetylglucosamine regulates p53 activity and stability
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DOI：
10.1038/ncb1470
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发表时间：
2006-10-01
影响因子：
21.3
通讯作者：
Cho, Jin Won
中科院分区：
文献类型：
--
作者：
Yang, Won Ho;Kim, Ji Eun;Cho, Jin Won
已知O-连接的N-乙酰葡糖胺（O-GlcNAc）翻译后添加到p53，但O-GlcNAc化的位点及其对p53的影响尚不清楚。在这里，我们表明，丝氨酸149的p53是O-GlcNAc酰化，这种修饰与减少磷酸化的p53在Thr 155，这是一个网站的目标是由COP 9信号体，导致减少p53泛素化。因此，在Ser 149处的O-GlcNAc化通过阻断泛素依赖性蛋白水解来稳定p53。我们的研究结果表明，O-GlcNAc和O-磷酸修饰之间的动态相互作用协调调节p53的稳定性和活性。
Post-translational addition of O-linked N-acetylglucosamine (O-GlcNAc) to p53 is known to occur, but the site of O-GlcNAcylation and its effects on p53 are not understood. Here, we show that Ser 149 of p53 is O-GlcNAcylated and that this modification is associated with decreased phosphorylation of p53 at Thr 155, which is a site that is targeted by the COP9 signalosome, resulting in decreased p53 ubiquitination. Accordingly, O-GlcNAcylation at Ser 149 stabilizes p53 by blocking ubiquitin-dependent proteolysis. Our results indicate that the dynamic interplay between O-GlcNAc and O-phosphate modifications coordinately regulate p53 stability and activity.