Journal
JOURNAL OF CELL BIOLOGY
Volume 201, Issue 4, Pages 511-521Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201210031
Keywords
-
Categories
Funding
- Grant Agency of the Czech Republic [P301/10/1525, P305/12/2485, 13-18392S]
- Academy of Sciences of the Czech Republic [RVO68378050]
- European Commission (Trireme and Biomedreg)
- Netherlands Genomic Initiative of Nederlandse organisatie voor Wetenschappelijk Onderzoek (Cancer Genomics Center)
- Dutch Cancer Society [UU2009-4478]
- Grant Agency of the Ministry of Health of the Czech Republic [NT13343-4]
- Charles University in Prague [PRVOUK-P27/LF1/1]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available