The type 2C phosphatase Wip1: an oncogenic regulator of tumor suppressor and DNA damage response pathways.
The type 2C phosphatase Wip1: an oncogenic regulator of tumor suppressor and DNA damage response pathways.
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DOI：
10.1007/s10555-008-9127-x
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发表时间：
2008-06
影响因子：
9.2
通讯作者：
Donehower, Lawrence A.
中科院分区：
文献类型：
--
作者：
Lu, Xiongbin;Nguyen, Thuy-Ai;Moon, Sung-Hwan;Darlington, Yolanda;Sommer, Matthias;Donehower, Lawrence A.
野生型p53诱导的磷酸酶1 Wip 1（或PPM 1D）的不寻常之处在于它是一种具有致癌活性的丝氨酸/苏氨酸磷酸酶。Wip 1是2C型磷酸酶（PP 2C δ）的成员，已显示在多种人类癌症类型（包括乳腺癌和卵巢癌）中扩增和过表达。在啮齿动物原代成纤维细胞转化试验中，Wip 1与已知的癌基因合作诱导转化灶。最近鉴定的Wip 1去磷酸化的靶蛋白提供了其致癌功能的机制见解。Wip 1通过使ATM和ATR（重要的DNA损伤传感器激酶）的底物蛋白质去磷酸化而作为DNA损伤反应的稳态调节剂。Wip 1还抑制多种肿瘤抑制因子的活性，包括p53、ATM、p16 INK 4a和ARF。我们目前的证据表明，抑制p53，p38 MAP激酶，ATM/ATR信号通路的Wip 1是其致癌性的重要组成部分，当它在人类癌症中扩增和过表达。
The Wild-type p53-induced phosphatase 1, Wip1 (or PPM1D), is unusual in that it is a serine/threonine phosphatase with oncogenic activity. A member of the type 2C phosphatases (PP2Cδ), Wip1 has been shown to be amplified and overexpressed in multiple human cancer types, including breast and ovarian carcinomas. In rodent primary fibroblast transformation assays, Wip1 cooperates with known oncogenes to induce transformed foci. The recent identification of target proteins that are dephosphorylated by Wip1 has provided mechanistic insights into its oncogenic functions. Wip1 acts as a homeostatic regulator of the DNA damage response by dephosphorylating proteins that are substrates of both ATM and ATR, important DNA damage sensor kinases. Wip1 also suppresses the activity of multiple tumor suppressors, including p53, ATM, p16INK4a and ARF. We present evidence that the suppression of p53, p38 MAP kinase, and ATM/ATR signaling pathways by Wip1 are important components of its oncogenicity when it is amplified and overexpressed in human cancers.
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影响因子：
64.8
作者：
Bartkova, J;Horejsi, Z;Bartek, J
通讯作者：
Bartek, J
影响因子：
11.4
作者：
Bulavin, DV;Saito, S;Fornace, AJ
通讯作者：
Fornace, AJ
影响因子：
64.8
作者：
DONEHOWER, LA;HARVEY, M;BRADLEY, A
通讯作者：
BRADLEY, A
DOI：
10.1073/pnas.94.12.6048
发表时间：
1997-06-10
影响因子：
11.1
作者：
Fiscella, M;Zhang, HL;Appella, E
通讯作者：
Appella, E
影响因子：
2.2
作者：
Fuku, Takeichi;Semba, Shuho;Yokozaki, Hiroshi
通讯作者：
Yokozaki, Hiroshi