PHLPPing through history: a decade in the life of PHLPP phosphatases.
PHLPPing through history: a decade in the life of PHLPP phosphatases.
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贯穿历史：PHLPP磷酸酶生命的十年。
DOI：
10.1042/bst20160170
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发表时间：
2016-12-15
影响因子：
3.9
通讯作者：
Newton AC
中科院分区：
文献类型：
--
作者：
Grzechnik AT;Newton AC
富含亮氨酸重复蛋白磷酸酶(PHLPP)在发现后的十年中已成为细胞内稳态的重要调节因子，其失调与多种病理生理机制有关，从癌症到糖尿病和心脏病等退行性疾病。PHLPP的两种同工酶PHLPP1和PHLPP2是在寻找使Akt去磷酸化从而抑制生长因子信号转导的磷酸酶时被鉴定出来的。然而，鉴于单个细胞中有超过20万个磷酸化残基，而Ser/Thr蛋白磷酸酶不到50个，因此PHLPP还有许多其他尚未被发现的细胞功能也就不足为奇了，包括最近发现的在调控表观基因组中的作用。PHLPP1和PHLPP2在人类癌症中普遍缺失，支持肿瘤抑制作用。相反，在糖尿病患者中，PHLPP1同工酶水平升高。因此，正确控制细胞内PHLPP活性的机制对于正常的细胞内稳态至关重要。本文就PHLPP的已知功能及其在疾病中的作用作一综述。
In the decade since their discovery, the PH domain Leucine rich repeat Protein Phosphatases (PHLPP) have emerged as critical regulators of cellular homeostasis and their dysregulation is associated with various pathophysiologies, ranging from cancer to degenerative diseases such as diabetes and heart disease. The two PHLPP isozymes, PHLPP1 and PHLPP2, were identified in a search for phosphatases that dephosphorylate Akt, and thus suppress growth factor signaling. However, given that there are over 200,000 phosphorylated residues in a single cell, and fewer than 50 Ser/Thr protein phosphatases, it is not surprising that PHLPP has many other cellular functions yet to be discovered, including a recently identified role in regulating the epigenome. Both PHLPP1 and PHLPP2 are commonly deleted in human cancers, supporting a tumor suppressive role. Conversely, the levels of one isozyme, PHLPP1, are elevated in diabetes. Thus, mechanisms to correctly control PHLPP activity in cells are critical for normal cellular homeostasis. This review summarizes the known functions of PHLPP and its role in disease.