The Pro-Oncogenic Adaptor CIN85 Acts as an Inhibitory Binding Partner of Hypoxia-Inducible Factor Prolyl Hydroxylase 2.
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
15 08 2019
15 08 2019
Historique:
received:
11
12
2018
revised:
17
04
2019
accepted:
24
05
2019
pubmed:
31
5
2019
medline:
17
6
2020
entrez:
31
5
2019
Statut:
ppublish
Résumé
The EGFR adaptor protein, CIN85, has been shown to promote breast cancer malignancy and hypoxia-inducible factor (HIF) stability. However, the mechanisms underlying cancer promotion remain ill defined. Here we show that CIN85 is a novel binding partner of the main HIF-prolyl hydroxylase, PHD2, but not of PHD1 or PHD3. Mechanistically, the N-terminal SRC homology 3 domains of CIN85 interacted with the proline-arginine-rich region within the N-terminus of PHD2, thereby inhibiting PHD2 activity and HIF degradation. This activity is essential
Identifiants
pubmed: 31142511
pii: 0008-5472.CAN-18-3852
doi: 10.1158/0008-5472.CAN-18-3852
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
SH3KBP1 protein, human
0
EGLN1 protein, human
EC 1.14.11.2
Hypoxia-Inducible Factor-Proline Dioxygenases
EC 1.14.11.29
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4042-4056Informations de copyright
©2019 American Association for Cancer Research.