Regulation of PP2A by Sphingolipid Metabolism and Signaling.

Regulation of PP2A by Sphingolipid Metabolism and Signaling.
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DOI:
10.3389/fonc.2014.00388
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发表时间:
2014
影响因子:
4.7
通讯作者:
Ogretmen B
Ogretmen B
中科院分区:
医学3区
文献类型:
--
作者:
Oaks J;Ogretmen B

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蛋白磷酸酶2A (PP2A)是一种丝氨酸/苏氨酸磷酸酶,通过靶向增殖激酶、细胞周期调节剂和细胞凋亡抑制剂,是细胞增殖的主要调节剂。正是通过这些调控元件的调控,PP2A才具有肿瘤抑制功能。除了调控亚基的突变外,由于内源性PP2A抑制剂如SET/I2PP2A的过表达或修饰,PP2A的磷酸酶/肿瘤抑制活性在几种癌症类型中也被抑制。本文综述了目前关于脂质信号分子、选择性鞘脂和PP2A抑制剂SET之间相互作用调控PP2A的文献,以及鞘脂作为PP2A激活剂通过靶向SET癌蛋白抑制肿瘤的治疗潜力。
Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase that is a primary regulator of cellular proliferation through targeting of proliferative kinases, cell cycle regulators, and apoptosis inhibitors. It is through the regulation of these regulatory elements that gives PP2A tumor suppressor functions. In addition to mutations on the regulatory subunits, the phosphatase/tumor suppressing activity of PP2A is also inhibited in several cancer types due to overexpression or modification of the endogenous PP2A inhibitors such as SET/I2PP2A. This review focuses on the current literature regarding the interactions between the lipid signaling molecules, selectively sphingolipids, and the PP2A inhibitor SET for the regulation of PP2A, and the therapeutic potential of sphingolipids as PP2A activators for tumor suppression via targeting SET oncoprotein.
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