Phosphorylation of the PTEN tail regulates protein stability and function
Phosphorylation of the PTEN tail regulates protein stability and function
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DOI：
10.1128/mcb.20.14.5010-5018.2000
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发表时间：
2000-07-01
影响因子：
5.3
通讯作者：
Sellers, WR
中科院分区：
文献类型：
--
作者：
Vazquez, F;Ramaswamy, S;Sellers, WR
PTEN基因是一种位于染色体10 q23区域的肿瘤抑制基因。PTEN蛋白（PTEN）的肿瘤抑制功能与其使脂质第二信使磷脂酰肌醇3，4，5-三磷酸和磷脂酰肌醇3，4-二磷酸去磷酸化的能力有关，并通过这样做拮抗磷酸肌醇3-激酶途径。PTEN蛋白由氨基末端磷酸酶结构域、脂质结合C2结构域和功能未知的50个氨基酸的C末端结构域（“尾”）组成。许多研究表明，尾巴是磷酸酶活性和阻断细胞生长的抑制剂。在这里，我们表明，PTEN尾是必要的，以维持蛋白质的稳定性，它也起到抑制PTEN功能。因此，去除尾部会导致稳定性的丧失，但不会导致功能丧失，因为所得蛋白质更具活性。此外，稳定性和活性的尾依赖性调节与尾内三个残基（S380、T382和T383）的磷酸化有关。因此，尾部可能通过磷酸化介导PTEN功能的调节。
The PTEN gene is a tumor suppressor localized in the frequently altered chromosomal region 10q23. The tumor suppressor function of the PTEN protein (PTEN) has been linked to its ability to dephosphorylate the lipid second-messenger phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3,4-bisphosphate and, by doing so, to antagonize the phosphoinositide 3-kinase pathway. The PTEN protein consists of an amino-terminal phosphatase domain, a lipid binding C2 domain, and a 50-amino-acid C-terminal domain (the ''tail") of unknown function. A number of studies have shown that the tail is dispensable for both phosphatase activity and blocking cell growth. Here, we show that the PTEN tail is necessary for maintaining protein stability and that it also acts to inhibit PTEN function. Thus, removing the tail results in a loss of stability but does not result in a loss of function because the resultant protein is more active. Furthermore, tail-dependent regulation of stability and activity is linked to the phosphorylation of three residues (S380, T382, and T383) within the tail. Therefore, the tail is likely to mediate the regulation of PTEN function through phosphorylation.