Negative control of CSL gene transcription by stress/DNA damage response and p53.

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State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_0562522E8266
Type
Article: article from journal or magazin.
Collection
Publications
Title
Negative control of CSL gene transcription by stress/DNA damage response and p53.
Journal
Cell Cycle
Author(s)
Menietti E., Xu X., Ostano P., Joseph J.M., Lefort K., Dotto G.P.
ISSN
1551-4005 (Electronic)
ISSN-L
1551-4005
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
15
Number
13
Pages
1767-1778
Language
english
Abstract
CSL is a key transcriptional repressor and mediator of Notch signaling. Despite wide interest in CSL, mechanisms responsible for its own regulation are little studied. CSL down-modulation in human dermal fibroblasts (HDFs) leads to conversion into cancer associated fibroblasts (CAF), promoting keratinocyte tumors. We show here that CSL transcript levels differ among HDF strains from different individuals, with negative correlation with genes involved in DNA damage/repair. CSL expression is negatively regulated by stress/DNA damage caused by UVA, Reactive Oxygen Species (ROS), smoke extract, and doxorubicin treatment. P53, a key effector of the DNA damage response, negatively controls CSL gene transcription, through suppression of CSL promoter activity and, indirectly, by increased p21 expression. CSL was previously shown to bind p53 suppressing its activity. The present findings indicate that p53, in turn, decreases CSL expression, which can serve to enhance p53 activity in acute DNA damage response of cells.
Keywords
CSL/RBPJ kappa, dermal fibroblasts, individual variations in gene transcription, p53, UVA/DNA damage response
Pubmed
Web of science
Create date
29/05/2016 14:12
Last modification date
20/08/2019 12:27
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