Multiple E3 ligases control tankyrase stability and function.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 11 2023
08 11 2023
Historique:
received:
22
05
2023
accepted:
26
10
2023
medline:
9
11
2023
pubmed:
8
11
2023
entrez:
8
11
2023
Statut:
epublish
Résumé
Tankyrase 1 and 2 are ADP-ribosyltransferases that catalyze formation of polyADP-Ribose (PAR) onto themselves and their binding partners. Tankyrase protein levels are regulated by the PAR-binding E3 ligase RNF146, which promotes K48-linked polyubiquitylation and proteasomal degradation of tankyrase and its partners. We identified a novel interaction between tankyrase and a distinct class of E3 ligases: the RING-UIM (Ubiquitin-Interacting Motif) family. We show that RNF114 and RNF166 bind and stabilize monoubiquitylated tankyrase and promote K11-linked diubiquitylation. This action competes with RNF146-mediated degradation, leading to stabilization of tankyrase and its binding partner, Angiomotin, a cancer cell signaling protein. Moreover, we identify multiple PAR-binding E3 ligases that promote ubiquitylation of tankyrase and induce stabilization or degradation. Discovery of K11 ubiquitylation that opposes degradation, along with identification of multiple PAR-binding E3 ligases that ubiquitylate tankyrase, provide insights into mechanisms of tankyrase regulation and may offer additional uses for tankyrase inhibitors in cancer therapy.
Identifiants
pubmed: 37938264
doi: 10.1038/s41467-023-42939-3
pii: 10.1038/s41467-023-42939-3
pmc: PMC10632493
doi:
Substances chimiques
Ubiquitin-Protein Ligases
EC 2.3.2.27
Tankyrases
EC 2.4.2.30
ADP Ribose Transferases
EC 2.4.2.-
Ribose
681HV46001
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
7208Subventions
Organisme : NIH HHS
ID : S10 OD010582
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016087
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM141292
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM129780
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2023. The Author(s).
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