The nuclear affairs of PTEN
The nuclear affairs of PTEN
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DOI：
10.1242/jcs.022459
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发表时间：
2008-02-01
影响因子：
4
通讯作者：
Eng, Charis
中科院分区：
文献类型：
--
作者：
Planchon, Sarah M.;Waite, Kristin A.;Eng, Charis
PTEN编码一种主要的肿瘤抑制蛋白，是一种双特异性磷酸酶。PTEN的失活已被证明与遗传性和散发性癌症有关。PTEN突变或缺失是历史上发现的最常见的肿瘤抑制基因失活机制，仅在少数散发性非培养原发癌中发现，这表明可能存在其他新的失活机制。尽管没有经典的核定位信号，但PTEN通过几种机制进入细胞核，包括简单扩散、主动穿梭、细胞质定位信号依赖的输出和单糖基化依赖的输入。细胞质PTEN是PI3K/AKT途径的负调控因子，但胞质PTEN与核PTEN不同。核PTEN在染色体稳定、DNA修复、细胞周期停滞和细胞稳定等方面发挥重要作用。这些功能之间的平衡是决定细胞是保持良性还是变成肿瘤的一个重要因素。
PTEN encodes a major tumor-suppressor protein that is a dual-specificity phosphatase. Inactivation of PTEN has been shown to be involved in heritable and sporadic cancers. Mutation or deletion of PTEN, historically the most commonly identified mechanisms of inactivation of tumor suppressors, is found only in the minority of sporadic non-cultured primary cancers, which indicates that there might be other, novel mechanisms of inactivation. Despite the absence of a classic nuclear localization signal, PTEN enters the nucleus by several mechanisms, including simple diffusion, active shuttling, cytoplasmic-localization-signal-dependent export and monoubiquitylation-dependent import. Cytoplasmic PTEN has a well-known role as a negative regulator of the PI3K/AKT pathway; however, it is becoming clear that cytosolic PTEN is not the same as nuclear PTEN. Nuclear PTEN plays a role in chromosome stability, DNA repair, cell cycle arrest and cellular stability. The balance between these functions is an important factor in determining whether a cell remains benign or becomes neoplastic.