ERAP1 promotes Hedgehog-dependent tumorigenesis by controlling USP47-mediated degradation of βTrCP.
Aminopeptidases
/ genetics
Animals
Carcinogenesis
/ genetics
Hedgehog Proteins
/ metabolism
Mice
Minor Histocompatibility Antigens
/ genetics
NIH 3T3 Cells
Protein Stability
Proteolysis
Signal Transduction
Ubiquitin-Specific Proteases
/ metabolism
beta-Transducin Repeat-Containing Proteins
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 07 2019
24 07 2019
Historique:
received:
14
08
2018
accepted:
18
06
2019
entrez:
26
7
2019
pubmed:
26
7
2019
medline:
11
2
2020
Statut:
epublish
Résumé
The Hedgehog (Hh) pathway is essential for embryonic development and tissue homeostasis. Aberrant Hh signaling may occur in a wide range of human cancers, such as medulloblastoma, the most common brain malignancy in childhood. Here, we identify endoplasmic reticulum aminopeptidase 1 (ERAP1), a key regulator of innate and adaptive antitumor immune responses, as a previously unknown player in the Hh signaling pathway. We demonstrate that ERAP1 binds the deubiquitylase enzyme USP47, displaces the USP47-associated βTrCP, the substrate-receptor subunit of the SCF
Identifiants
pubmed: 31341163
doi: 10.1038/s41467-019-11093-0
pii: 10.1038/s41467-019-11093-0
pmc: PMC6656771
doi:
Substances chimiques
Hedgehog Proteins
0
Minor Histocompatibility Antigens
0
beta-Transducin Repeat-Containing Proteins
0
Aminopeptidases
EC 3.4.11.-
ERAP1 protein, mouse
EC 3.4.11.-
Ubiquitin-Specific Proteases
EC 3.4.19.12
Usp47 protein, mouse
EC 3.4.19.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3304Subventions
Organisme : Medical Research Council
ID : MC_U132670600
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00025/2
Pays : United Kingdom
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