Westermarck Jukka, Hahn William C
Institute of Medical Technology, University of Tampere and Tampere University Hospital, 33520 Tampere, Finland.
Trends Mol Med. 2008 Apr;14(4):152-60. doi: 10.1016/j.molmed.2008.02.001. Epub 2008 Mar 10.
Reversible protein phosphorylation plays a central role in regulating intracellular signaling. Dysregulation of the mechanisms that regulate phosphorylation plays a direct role in cancer initiation and maintenance. Although abundant evidence supports the role of kinase oncogenes in cancer development, recent work has illuminated the role of specific protein phosphatases in malignant transformation. Protein phosphatase 2A (PP2A) is the major serine-threonine phosphatase in mammalian cells. Inactivation of PP2A by viral oncoproteins, mutation of specific subunits or overexpression of endogenous inhibitors contributes to cell transformation by regulating specific phosphorylation events. Here, we review recent progress in our understanding of how PP2A regulates mitogenic signaling pathways in cancer pathogenesis and how PP2A activity is modulated in human cancers.
可逆性蛋白质磷酸化在调节细胞内信号传导中起核心作用。调节磷酸化的机制失调在癌症的发生和维持中起直接作用。尽管有大量证据支持激酶癌基因在癌症发展中的作用，但最近的研究揭示了特定蛋白磷酸酶在恶性转化中的作用。蛋白磷酸酶2A（PP2A）是哺乳动物细胞中的主要丝氨酸 - 苏氨酸磷酸酶。病毒癌蛋白使PP2A失活、特定亚基的突变或内源性抑制剂的过表达通过调节特定的磷酸化事件促进细胞转化。在此，我们综述了我们对PP2A如何在癌症发病机制中调节有丝分裂信号通路以及PP2A活性在人类癌症中如何被调节的最新认识进展。
