OTUD7B Activates Wnt Signaling Pathway through the Interaction with LEF1.
LEF1
OTUD7B
Wnt signaling
β-catenin
Journal
Biomolecules
ISSN: 2218-273X
Titre abrégé: Biomolecules
Pays: Switzerland
ID NLM: 101596414
Informations de publication
Date de publication:
16 06 2023
16 06 2023
Historique:
received:
06
05
2023
revised:
04
06
2023
accepted:
14
06
2023
medline:
29
6
2023
pubmed:
28
6
2023
entrez:
28
6
2023
Statut:
epublish
Résumé
The Wnt signaling pathway plays a critical role in regulating normal cellular processes, including proliferation, differentiation, and apoptosis. Dysregulation of Wnt signaling has been implicated in various human diseases, including cancer. β-catenin and LEF1 are key mediators of Wnt signaling, and their dysregulation is a hallmark of many cancer types. In this study, we aimed to identify the deubiquitinases (DUBs) that regulate the Wnt signaling pathway through the essential component LEF1. Screening candidate DUBs from the human DUB library, we discovered that OTUD7B interacts with LEF1 and activates Wnt signaling. OTUD7B and LEF1 interact with each other through the UBA and HMG domains, respectively. Furthermore, OTUD7B promotes the nuclear localization of LEF1, leading to an increased interaction with β-catenin in the nucleus while not noticeably affecting ubiquitination on LEF1. Using qPCR array analysis, we found that OTUD7B overexpression leads to an upregulation of 75% of the tested Wnt target genes compared to the control. These findings suggest that OTUD7B may serve as a potential therapeutic target in human diseases, including cancers where Wnt signaling is frequently dysregulated.
Identifiants
pubmed: 37371581
pii: biom13061001
doi: 10.3390/biom13061001
pmc: PMC10295924
pii:
doi:
Substances chimiques
beta Catenin
0
OTUD7B protein, human
EC 3.4.-
Endopeptidases
EC 3.4.-
LEF1 protein, human
0
Lymphoid Enhancer-Binding Factor 1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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