Autophagy Controls CSL/RBPJκ Stability through a p62/SQSTM1-Dependent Mechanism.

Détails

Ressource 1Télécharger: 1-s2.0-S2211124718313147-main.pdf (2550.04 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_4A74051ADE12
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Autophagy Controls CSL/RBPJκ Stability through a p62/SQSTM1-Dependent Mechanism.
Périodique
Cell reports
Auteur(s)
Goruppi S., Jo S.H., Laszlo C., Clocchiatti A., Neel V., Dotto G.P.
ISSN
2211-1247 (Electronic)
Statut éditorial
Publié
Date de publication
18/09/2018
Peer-reviewed
Oui
Volume
24
Numéro
12
Pages
3108-3114.e4
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Cancer-associated fibroblasts (CAFs) are important at all tumor stages. CSL/RBPJκ suppresses the gene expression program leading to CAF activation and associated metabolic reprogramming, as well as autophagy. Little is known about CSL protein turnover, especially in the tumor microenvironment. We report that, in human dermal fibroblasts (HDFs), conditions inducing autophagy-often found in tumor stroma-down-regulate CSL protein levels but do not affect its mRNA levels. Genetic or pharmacologic targeting of the autophagic machinery blocks CSL down-modulation. Mechanistically, endogenous CSL associates with the autophagy and signaling adaptor p62/SQSTM1, which is required for CSL down-modulation by autophagy. This is functionally significant, because both CSL and p62 levels are lower in skin cancer-derived CAFs, in which autophagy is increased. Increasing cellular CSL levels stabilizes p62 and down-modulates the autophagic process. We reveal here an autophagy-initiated mechanism for CSL down-modulation, which could be targeted for stroma-focused cancer prevention and treatment.
Mots-clé
CAF, CSL/RBPJκ, autophagy, cancer-associated fibroblast, p62/SQSTM1, protein turnover
Pubmed
Web of science
Open Access
Oui
Création de la notice
08/10/2018 8:01
Dernière modification de la notice
20/08/2019 13:58
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