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

Détails

Ressource 1Télécharger: BIB_0562522E8266.P001.pdf (3086.04 [Ko])
Etat: Serval
Version: Author's accepted manuscript
ID Serval
serval:BIB_0562522E8266
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Negative control of CSL gene transcription by stress/DNA damage response and p53.
Périodique
Cell Cycle
Auteur(s)
Menietti E., Xu X., Ostano P., Joseph J.M., Lefort K., Dotto G.P.
ISSN
1551-4005 (Electronic)
ISSN-L
1551-4005
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
15
Numéro
13
Pages
1767-1778
Langue
anglais
Résumé
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.
Mots-clé
CSL/RBPJ kappa, dermal fibroblasts, individual variations in gene transcription, p53, UVA/DNA damage response
Pubmed
Web of science
Création de la notice
29/05/2016 15:12
Dernière modification de la notice
03/03/2018 13:24
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