Reconstitution of the destruction complex defines roles of AXIN polymers and APC in β-catenin capture, phosphorylation, and ubiquitylation.
SCF(β-TrCP)
Wnt/beta-catenin signalling
adenomatous polyposis coli (APC)
axis inhibition protein (AXIN)
beta-catenin destruction complex
biochemistry
casein kinase 1 (CK1)
colorectal cancer
glycogen synthase kinase 3 (GSK3)
ubiquitin
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
19 08 2021
19 08 2021
Historique:
received:
13
07
2020
revised:
18
05
2021
accepted:
13
07
2021
pubmed:
6
8
2021
medline:
2
9
2021
entrez:
5
8
2021
Statut:
ppublish
Résumé
The Wnt/β-catenin pathway is a highly conserved, frequently mutated developmental and cancer pathway. Its output is defined mainly by β-catenin's phosphorylation- and ubiquitylation-dependent proteasomal degradation, initiated by the multi-protein β-catenin destruction complex. The precise mechanisms underlying destruction complex function have remained unknown, largely because of the lack of suitable in vitro systems. Here we describe the in vitro reconstitution of an active human β-catenin destruction complex from purified components, recapitulating complex assembly, β-catenin modification, and degradation. We reveal that AXIN1 polymerization and APC promote β-catenin capture, phosphorylation, and ubiquitylation. APC facilitates β-catenin's flux through the complex by limiting ubiquitylation processivity and directly interacts with the SCF
Identifiants
pubmed: 34352208
pii: S1097-2765(21)00582-7
doi: 10.1016/j.molcel.2021.07.013
pmc: PMC8403986
pii:
doi:
Substances chimiques
APC protein, human
0
AXIN1 protein, human
0
Adenomatous Polyposis Coli Protein
0
Axin Protein
0
CTNNB1 protein, human
0
Multiprotein Complexes
0
beta Catenin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3246-3261.e11Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C47521/A28286
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C47521/A16217
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 214311/Z/18/Z
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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