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Abstract：
Whereas protein kinases have been successfully targeted for a variety of diseases, protein phosphatases remain an underutilized therapeutic target, in part because of incomplete characterization of their effects on signaling networks. The pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) is a relatively new player in the cell signaling field, and new roles in controlling the balance among cell survival, proliferation, and apoptosis are being increasingly identified. Originally characterized for its tumor-suppressive function in deactivating the prosurvival kinase Akt, PHLPP may have an opposing role in promoting survival, as recent evidence suggests. Additionally, identification of the transcription factor STAT1 as a substrate unveils a role for PHLPP as a critical mediator of transcriptional programs in cancer and the inflammatory response. This review summarizes the current knowledge of PHLPP as both a tumor suppressor and an oncogene and highlights emerging functions in regulating gene expression and the immune system. Understanding the context-dependent functions of PHLPP is essential for appropriate therapeutic intervention.
摘要：
而蛋白激酶已成功地靶向多种疾病，蛋白磷酸酶仍然是一个未充分利用的治疗靶点，部分原因是它们对信令网络的影响的表征不完整。pleckstrin同源域富含亮氨酸重复蛋白磷酸酶(PHLPP)是细胞信号领域中一个相对较新的参与者,以及控制细胞存活平衡的新角色，扩散,和细胞凋亡越来越被识别。最初的特征是其在灭活前生存激酶Akt中的肿瘤抑制功能，PHLPP在促进生存方面可能有相反的作用，正如最近的证据所表明的。此外,转录因子STAT1作为底物的鉴定揭示了PHLPP作为癌症和炎症反应中转录程序的关键介质的作用。这篇综述总结了PHLPP作为肿瘤抑制因子和癌基因的最新知识，并强调了在调节基因表达和免疫系统方面的新兴功能。了解PHLPP的上下文相关功能对于适当的治疗干预至关重要。
