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首页> 外文期刊>Cancer Cell >Lack of PTEN sequesters CHK1 and initiates genetic instability.
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Lack of PTEN sequesters CHK1 and initiates genetic instability.

机译:PTEN的缺乏会隔离CHK1并引发遗传不稳定。

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摘要

Pten-/- cells display a partially defective checkpoint in response to ionizing radiation (IR). The checkpoint defect was traced to the ability of AKT to phosphorylate CHK1 at serine 280, since a nonphosphorylated mutant of CHK1 (S280A) complemented the checkpoint defect and restored CDC25A degradation. CHK1 phosphorylation at serine 280 led to covalent binding of 1 to 2 molecules of ubiquitin and cytoplasmic CHK1 localization. Primary breast carcinomas lacking PTEN expression and having elevated AKT phosphorylation had increased cytoplasmic CHK1 and displayed aneuploidy (p <0.005). We conclude that loss of PTEN and subsequent activation of AKT impair CHK1 through phosphorylation, ubiquitination, and reduced nuclear localization to promote genomic instability in tumor cells.
机译:Pten //-细胞响应电离辐射(IR)会显示部分缺陷的检查点。检查点缺陷可追溯到AKT在丝氨酸280磷酸化CHK1的能力,因为CHK1的非磷酸化突变体(S280A)补充了检查点缺陷并恢复了CDC25A降解。丝氨酸280上的CHK1磷酸化导致1-2泛素分子的共价结合和细胞质CHK1定位。缺乏PTEN表达且AKT磷酸化水平升高的原发性乳腺癌细胞质CHK1增加,并显示非整倍性(p <0.005)。我们得出结论,PTEN的丧失和随后AKT的激活会通过磷酸化,泛素化和减少的核定位来促进肿瘤细胞中的基因组不稳定,从而损害CHK1。

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