Gain-of-function mutations of PPM1D/Wip1 impair the p53-dependent G1 checkpoint.
Gain-of-function mutations of PPM1D/Wip1 impair the p53-dependent G1 checkpoint.
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DOI：
10.1083/jcb.201210031
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发表时间：
2013-05-13
期刊：
影响因子：
--
通讯作者：
Macurek L
中科院分区：
文献类型：
--
作者：
Kleiblova P;Shaltiel IA;Benada J;Ševčík J;Pecháčková S;Pohlreich P;Voest EE;Dundr P;Bartek J;Kleibl Z;Medema RH;Macurek L
Mutations in PPM1D/Wip1 phosphatase impair the DNA damage-induced checkpoint and may predispose cells to tumorigenesis. The DNA damage response (DDR) pathway and its core component tumor suppressor p53 block cell cycle progression after genotoxic stress and represent an intrinsic barrier preventing cancer development. The serine/threonine phosphatase PPM1D/Wip1 inactivates p53 and promotes termination of the DDR pathway. Wip1 has been suggested to act as an oncogene in a subset of tumors that retain wild-type p53. In this paper, we have identified novel gain-of-function mutations in exon 6 of PPM1D that result in expression of C-terminally truncated Wip1. Remarkably, mutations in PPM1D are present not only in the tumors but also in other tissues of breast and colorectal cancer patients, indicating that they arise early in development or affect the germline. We show that mutations in PPM1D affect the DDR pathway and propose that they could predispose to cancer.
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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：
64.8
作者：
Bartkova, Jirina;Rezaei, Nousin;Gorgoulis, Vassilis G.
通讯作者：
Gorgoulis, Vassilis G.
影响因子：
64.8
作者：
Di Micco, Raffaella;Fumagalli, Marzia;di Fagagna, Fabrizio d'Adda
通讯作者：
di Fagagna, Fabrizio d'Adda
影响因子：
64.5
作者：
ELDEIRY, WS;TOKINO, T;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
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