Structure, Regulation, and Pharmacological Modulation of PP2A Phosphatases
Structure, Regulation, and Pharmacological Modulation of PP2A Phosphatases
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DOI：
10.1007/978-1-62703-562-0_17
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发表时间：
2013-01-01
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影响因子：
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通讯作者：
Janssens, Veerle
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文献类型：
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作者：
Lambrecht, Caroline;Haesen, Dorien;Janssens, Veerle
2A型蛋白磷酸酶家族(PP2A)在任何特定的人体组织中都是细胞Ser/Thr磷酸酶活性的主要组成部分。在这篇综述中，我们描述了PP2A的全酶性质和几个不同的PP2A组成亚基的存在如何允许产生多个结构和功能不同的PP2A复合体，解释了为什么PP2A参与了如此多不同的细胞生物学和生理过程的调节。此外，在人类疾病中，最明显的是在几种癌症和阿尔茨海默病中，PP2A的表达和/或活性已被发现显著降低，这突显了其作为主要肿瘤抑制因子和tau磷酸酶的重要功能。因此，最近的一些临床前研究表明，在一定条件下，药理上恢复PP2A活性，以及药理上抑制PP2A，可能具有重要的未来治疗价值。
Protein phosphatases of the type 2A family (PP2A) represent a major fraction of cellular Ser/Thr phosphatase activity in any given human tissue. In this review, we describe how the holoenzymic nature of PP2A and the existence of several distinct PP2A composing subunits allow for the generation of multiple structurally and functionally different PP2A complexes, explaining why PP2A is involved in the regulation of so many diverse cell biological and physiological processes. Moreover, in human disease, most notably in several cancers and Alzheimer's Disease, PP2A expression and/or activity have been found significantly decreased, underscoring its important functions as a major tumor suppressor and tau phosphatase. Hence, several recent preclinical studies have demonstrated that pharmacological restoration of PP2A activity, as well as pharmacological PP2A inhibition, under certain conditions, may be of significant future therapeutic value.