Gain-of-function mutations of PPM1D/Wip1 impair the p53-dependent G1 checkpoint

Kleiblová, P.; Shaltiel, I.A.; Benada, Jan; Ševčík, J.; Pecháčková, Soňa; Pohlreich, P.; Voest, E.E.; Dundr, P.; Bártek, Jiří; Kleibl, Z.; Medema, R.H.; Macůrek, Libor

doi:https://dx.doi.org/10.1083/jcb.201210031

Number of the records: 1

Gain-of-function mutations of PPM1D/Wip1 impair the p53-dependent G1 checkpoint

1.

SYSNO ASEP	0423172
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Gain-of-function mutations of PPM1D/Wip1 impair the p53-dependent G1 checkpoint
Author(s)	Kleiblová, P. (CZ) Shaltiel, I.A. (NL) Benada, Jan (UMG-J) Ševčík, J. (CZ) Pecháčková, Soňa (UMG-J) Pohlreich, P. (CZ) Voest, E.E. (NL) Dundr, P. (CZ) Bártek, Jiří (UMG-J)_RID Kleibl, Z. (CZ) Medema, R.H. (NL) Macůrek, Libor (UMG-J)_{RID, ORCID}
Source Title	Journal of Cell Biology. - : Rockefeller University Press - ISSN 0021-9525 Roč. 201, č. 4 (2013), s. 511-521
Number of pages	11 s.
Language	eng - English
Country	US - United States
Keywords	DNA damage ; cell cycle ; cancer
Subject RIV	EB - Genetics ; Molecular Biology
R&D Projects	GAP301/10/1525 GA ČR - Czech Science Foundation (CSF)
	GAP305/12/2485 GA ČR - Czech Science Foundation (CSF)
	GA13-18392S GA ČR - Czech Science Foundation (CSF)
Institutional support	UMG-J - RVO:68378050
UT WOS	000318909500005
DOI	10.1083/jcb.201210031
Annotation	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.
Workplace	Institute of Molecular Genetics
Contact	Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217
Year of Publishing	2014

Number of the records: 1