PHOSPHORYLATION AT SER-15 AND SER-392 IN MUTANT P53-MOLECULES FROM HUMAN TUMORS IS ALTERED COMPARED TO WILD-TYPE P53
PHOSPHORYLATION AT SER-15 AND SER-392 IN MUTANT P53-MOLECULES FROM HUMAN TUMORS IS ALTERED COMPARED TO WILD-TYPE P53
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DOI：
10.1073/pnas.90.13.5954
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发表时间：
1993-07-01
影响因子：
11.1
通讯作者：
APPELLA, E
中科院分区：
文献类型：
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作者：
ULLRICH, SJ;SAKAGUCHI, K;APPELLA, E
p53 基因的产物抑制细胞生长，在抑制人类肿瘤的发展中发挥着关键作用。 p53 蛋白结合 DNA，激活转录，并可在 N 端和 C 端位点磷酸化。此前，在 p53 介导的体内生长停滞期间，野生型 p53 与突变型 p53 相比被过度磷酸化。在这里，我们证明野生型人 p53 N 端反式激活结构域中的 Ser-15 和 Ser-9 在源自人胶质母细胞瘤系 T98G 的细胞体内被磷酸化。在[Ile237]p53和[Ala143]p53（来自人类肿瘤的两种天然p53突变体，它们转录激活有缺陷）中，与野生型p53相比，Ser-15的磷酸化减少，Ser-392的磷酸化增加。 Ser-9 没有观察到变化。 [His273]p53，第三个突变体，具有与野生型p53相似的磷酸化状态。我们认为 Ser-15 的磷酸化可能取决于 p53 采用野生型构象的能力，并且可能有助于 p53 阻止细胞生长的能力。
The product of the p53 gene suppresses cell growth and plays a critical role in suppressing development of human tumors. p53 protein binds DNA, activates transcription, and can be phosphorylated at N- and C-terminal sites. Previously, wild-type p53 was shown to be hyperphosphorylated compared to mutant p53 during p53-mediated growth arrest in vivo. Here we show that Ser-15 and Ser-9 in the N-terminal transactivation domain of wild-type human p53 are phosphorylated in vivo in cells derived from the human glioblastoma line T98G. In [Ile237]p53 and [Ala143]p53, two natural p53 mutants from human tumors that are defective for activation of transcription, phosphorylation at Ser-15 was reduced and phosphorylation at Ser-392 was increased compared to wild-type p53. No change was observed at Ser-9. [His273]p53, a third mutant, had a phosphorylation state similar to that of wild-type p53. We suggest that phosphorylation of Ser-15 may depend on the ability of p53 to adopt a wild-type conformation and may contribute to p53's ability to block cell growth.