抑癌蛋白PTEN及PDZ蛋白对其的调节

pten基因是迄今为止发现的第1个具有双特异性磷酸酶活性的抑癌基因，该基因的编码产物PTEN蛋白,是具有蛋白与脂质磷酸酯酶活性的双特异性磷酸酯酶，作为1种重要的信号分子参与细胞增殖、分化、黏附、迁移、凋亡以及基因转录的调控. 最近，关于PTEN在信号转导中的作用以及细胞内PTEN的调节机制研究较多，尤其是PDZ蛋白对PTEN的调节作用. PTEN蛋白包括1个氨基端（N端）磷酸酯酶区域，1个与脂质结合的C2区域和1个含有PDZ结合序列的羧基端（C端）区域. PDZ结构域通过识别目标蛋白羧基端PDZ结合序列与目标蛋白相互作用，调控多种重要的细胞生理过程和信号传导途径.本文就抑癌基因pten编码产物PTEN蛋白的结构、PTEN的生物学功能和PDZ蛋白对PTEN调节的研究进展进行综述.

Regulation of PTEN Tumor Suppressor by PDZ Proteins

PDZ is a modular protein interaction domain that mostly recognizes the C-terminal motifs of its target proteins, and plays important roles in protein targeting and/or protein complex assembling in various cell signaling pathways. PTEN (phosphatase and tensin homologue deleted on chromosome 10) is composed of an N-terminal phosphatase domain, a C2 domain and a class I PDZ binding motif at the C-terminus. As a unique tumor suppressor gene that encodes a phosphatase with dual catalytic specificity, PTEN is able to dephosphorylates both lipid and protein substrates and is known to antagonize the phosphatidyl inositol 3-kinase (PI3K) activity by hydrolyzing the 3′phosphate of phosphoinositides. Recently, the intracellular modulation of PTEN, especially by PDZ proteins, and its critical roles in cell signaling are intensively investigated, which in turn deepened the understanding of PTEN functions in cell cycle progression, metabolism, migration, apoptosis and gene regulations. This review will discuss the molecular structure of PTEN in relation to its biological functions, particularly focusing on the recent research progress in the regulated PTEN activity by PDZ proteins.