Repression of Wnt/β-catenin signaling by SOX9 and Mastermind-like transcriptional coactivator 2.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
30
07
2020
accepted:
05
01
2021
entrez:
18
2
2021
pubmed:
19
2
2021
medline:
19
4
2022
Statut:
epublish
Résumé
Wnt/β-catenin signaling requires inhibition of a multiprotein destruction complex that targets β-catenin for proteasomal degradation. SOX9 is a potent antagonist of the Wnt pathway and has been proposed to act through direct binding to β-catenin or the β-catenin destruction complex. Here, we demonstrate that SOX9 promotes turnover of β-catenin in mammalian cell culture, but this occurs independently of the destruction complex and the proteasome. This activity requires SOX9's ability to activate transcription. Transcriptome analysis revealed that SOX9 induces the expression of the Notch coactivator Mastermind-like transcriptional activator 2 (MAML2), which is required for SOX9-dependent Wnt/β-catenin antagonism. MAML2 promotes β-catenin turnover independently of Notch signaling, and MAML2 appears to associate directly with β-catenin in an in vitro binding assay. This work defines a previously unidentified pathway that promotes β-catenin degradation, acting in parallel to established mechanisms. SOX9 uses this pathway to restrict Wnt/β-catenin signaling.
Identifiants
pubmed: 33597243
pii: 7/8/eabe0849
doi: 10.1126/sciadv.abe0849
pmc: PMC7888933
pii:
doi:
Substances chimiques
SOX9 Transcription Factor
0
beta Catenin
0
Proteasome Endopeptidase Complex
EC 3.4.25.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM108468
Pays : United States
Organisme : NIGMS NIH HHS
ID : R15 GM101598
Pays : United States
Informations de copyright
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
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