Lysine Demethylase KDM2A Promotes Proteasomal Degradation of TCF/LEF Transcription Factors in a Neddylation-Dependent Manner.
KDM2A
TCF/LEF
canonical Wnt signaling
neddylation
ubiquitination
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
13 Nov 2023
13 Nov 2023
Historique:
received:
20
09
2023
revised:
02
11
2023
accepted:
10
11
2023
medline:
27
11
2023
pubmed:
24
11
2023
entrez:
24
11
2023
Statut:
epublish
Résumé
Canonical Wnt signaling is essential for a plethora of biological processes ranging from early embryogenesis to aging. Malfunctions of this crucial signaling pathway are associated with various developmental defects and diseases, including cancer. Although TCF/LEF transcription factors (TCF/LEFs) are known to be essential for this pathway, the regulation of their intracellular levels is not completely understood. Here, we show that the lysine demethylase KDM2A promotes the proteasomal destabilization of TCF/LEFs independently of its demethylase domain. We found that the KDM2A-mediated destabilization of TCF/LEFs is dependent on the KDM2A zinc finger CXXC domain. Furthermore, we identified the C-terminal region of TCF7L2 and the CXXC domain of KDM2A as the domains responsible for the interaction between the two proteins. Our study is also the first to show that endogenous TCF/LEF proteins undergo KDM2A-mediated proteasomal degradation in a neddylation-dependent manner. Here, we reveal a completely new mechanism that affects canonical Wnt signaling by regulating the levels of TCF/LEF transcription factors through their KDM2A-promoted proteasomal degradation.
Identifiants
pubmed: 37998355
pii: cells12222620
doi: 10.3390/cells12222620
pmc: PMC10670284
pii:
doi:
Substances chimiques
Lysine
K3Z4F929H6
beta Catenin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Charles University
ID : Cooperatio - Oncology and Hematology
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