GSK3β N-terminus binding to p53 promotes its acetylation
GSK3β N-terminus binding to p53 promotes its acetylation
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DOI：
10.1186/1476-4598-8-14
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发表时间：
2009-03-05
期刊：
影响因子：
37.3
通讯作者：
Jope, Richard S.
中科院分区：
文献类型：
--
作者：
Eom, Tae-Yeon;Jope, Richard S.
p53突变在人类癌症中的普遍存在例证了其作为肿瘤抑制转录因子的关键作用。先前的研究表明，组成型活性丝氨酸/苏氨酸激酶糖原合成酶激酶-3 β（GSK 3 β）与p53的C-末端碱性结构域缔合并调节其作用。在这项研究中，我们确定了GSK 3 β N-末端氨基酸78 - 92为必要的与p53的关联。GSK 3抑制剂损害p53中GSK 3 β结合区附近Lys 373和Lys 382处的p53乙酰化，表明GSK 3 β促进p53乙酰化。我们还发现p53的乙酰化减少了它与GSK 3 β以及GSK 3 α的结合。这些结果表明，GSK 3 β的N-末端区域结合p53，这种结合促进p53的乙酰化，随后乙酰化的p53从GSK 3解离。
The prevalence in human cancers of mutations in p53 exemplifies its crucial role as a tumor suppressor transcription factor. Previous studies have shown that the constitutively active serine/threonine kinase glycogen synthase kinase-3 beta (GSK3 beta) associates with the C-terminal basic domain of p53 and regulates its actions. In this study we identified the GSK3 beta N-terminal amino acids 78 92 as necessary for its association with p53. Inhibitors of GSK3 impaired the acetylation of p53 at Lys373 and Lys382 near the GSK3 beta binding region in p53, indicating that GSK3 beta facilitates p53 acetylation. We also found that acetylation of p53 reduced its association with GSK3 beta, as well as with GSK3 alpha. These results indicate that the N-terminal region of GSK3 beta binds p53, this association promotes the acetylation of p53, and subsequently acetylated p53 dissociates from GSK3.