Phosphatase: PP2A structural importance, regulation and its aberrant expression in cancer.
Phosphatase: PP2A structural importance, regulation and its aberrant expression in cancer.
复制标题
DOI：
10.1016/j.canlet.2013.02.036
复制
发表时间：
2013-07-10
期刊：
影响因子：
9.7
通讯作者：
Batra, Surinder K.
中科院分区：
文献类型：
--
作者：
Seshacharyulu, Parthasarathy;Pandey, Poomy;Datta, Kaustubh;Batra, Surinder K.
关键词：
蛋白质磷酸酶2A（PP 2A）是一种重要的丝氨酸苏氨酸磷酸酶，广泛表达，通过去磷酸化Akt、p53、c-Myc和β-catenin等重要的细胞分子来调节其功能。它在细胞增殖、信号转导和凋亡等细胞过程中起着关键作用。在结构上，它是多种多样的，因为它是由催化，支架和调节亚基。催化亚基和支架亚基具有两种同种型，调节亚基具有包含不同同种型的四个不同家族。调节亚基是最多样的，具有时间和空间特异性。PP 2A经历翻译后修饰（即磷酸化和甲基化），这反过来又调节其酶活性。PP 2A支架和调节亚基的异常表达、突变和体细胞改变已经在各种人类恶性肿瘤中观察到，包括肺癌、乳腺癌、皮肤癌和结肠癌，突出了其作为“肿瘤抑制剂”的作用。本文综述了丝氨酸/苏氨酸磷酸酶PP 2A的结构复杂性及其在肿瘤中的表达模式。此外，PP 2A相互作用和调节蛋白和底物也进行了讨论。最后，本文还对PP 2A亚基在体内模型系统中的生物学作用的小鼠模型进行了综述。
Protein Phosphatase 2A (PP2A) is an important and ubiquitously expressed serine threonine phosphatase and regulates the function by dephosphorylating many critical cellular molecules like Akt, p53, c-Myc and β-catenin. It plays a critical role in cellular processes, such as cell proliferation, signal transduction and apoptosis. Structurally, it is multifarious as it is composed of catalytic, scaffold and regulatory subunits. The catalytic and scaffold subunits have two isoforms and the regulatory subunit has four different families containing different isoforms. The regulatory subunit is the most diverse with temporal and spatial specificity. PP2A undergoes post-translational modifications (i.e. phosphorylation and methylation), which in turn, regulates its enzymatic activity. Aberrant expression, mutations and somatic alterations of the PP2A scaffold and regulatory subunits have been observed in various human malignancies, including lung, breast, skin and colon cancer, highlighting its role as a ‘tumor suppressor’. This review is focused on the structural complexity of serine/threonine phosphatase PP2A and summarizes its expression pattern in cancer. Additionally, the PP2A interacting and regulatory proteins and substrates are also discussed. Finally, the mouse models developed to understand the biological role of PP2A subunits in an in vivo model system are also reviewed in this article.
登录
查看更多内容
影响因子：
1.9
作者：
Cheng Y;Liu W;Kim ST;Sun J;Lu L;Sun J;Zheng SL;Isaacs WB;Xu J
通讯作者：
Xu J
影响因子：
6.2
作者：
Dupont, William D.;Breyer, Joan P.;Bradley, Kevin M.;Schuyler, Peggy A.;Plummer, W. Dale;Sanders, Melinda E.;Page, David L.;Smith, Jeffrey R.
通讯作者：
Smith, Jeffrey R.
DOI：
10.1073/pnas.85.12.4252
发表时间：
1988-06-01
影响因子：
11.1
作者：
ARINO, J;CHEE, WW;JOHNSON, GL
通讯作者：
JOHNSON, GL
DOI：
10.1152/ajplung.00262.2001
发表时间：
2002-06-01
影响因子：
4.9
作者：
Everett, AD;Kamibayashi, C;Brautigan, DL
通讯作者：
Brautigan, DL
影响因子：
64.8
作者：
Cho, Uhn Soo;Xu, Wenqing
通讯作者：
Xu, Wenqing