Phosphorylation-regulated cleavage of the tumor suppressor PTEN by caspase-3 - Implications for the control of protein stability and PTEN-protein interactions
Phosphorylation-regulated cleavage of the tumor suppressor PTEN by caspase-3 - Implications for the control of protein stability and PTEN-protein interactions
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DOI：
10.1074/jbc.m212610200
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发表时间：
2003-08-15
影响因子：
4.8
通讯作者：
Pulido, R
中科院分区：
文献类型：
--
作者：
Torres, J;Rodriguez, J;Pulido, R
PTEN磷酸酶是人类癌症中最常见的靶向肿瘤抑制因子之一，是细胞生长和凋亡的关键调节因子。我们发现PTEN被caspase-3在多个靶点切割，位于分子C末端的非结构区域。经肿瘤坏死因子α细胞处理后，PTEN的裂解增加，并受蛋白激酶CK2对PTEN C末端尾部的磷酸化的负调控。蛋白水解性PTEN片段的蛋白质稳定性降低，与PTEN相互作用的支架蛋白S-SCAM/MAGI-2相互作用的能力丧失。有趣的是，S-SCAM/MAGI-2也被Caspase-3切割。我们的研究结果表明，在细胞凋亡过程中，存在一种调节蛋白质稳定性和PTEN-蛋白质相互作用的机制，这种调节机制由caspase-3以PTEN磷酸化调节的方式执行。
PTEN phosphatase is one of the most commonly targeted tumor suppressors in human cancers and a key regulator of cell growth and apoptosis. We have found that PTEN is cleaved by caspase-3 at several target sites, located in unstructured regions within the C terminus of the molecule. Cleavage of PTEN was increased upon TNFalpha-cell treatment and was negatively regulated by phosphorylation of the C-terminal tail of PTEN by the protein kinase CK2. The proteolytic PTEN fragments displayed reduced protein stability, and their capability to interact with the PTEN interacting scaffolding protein S-SCAM/MAGI-2 was lost. Interestingly, S-SCAM/MAGI-2 was also cleaved by caspase-3. Our findings suggest the existence of a regulatory mechanism of protein stability and PTEN-protein interactions during apoptosis, executed by caspase-3 in a PTEN phosphorylation-regulated manner.