publication . Article . Other literature type . 2019

The Pro-Oncogenic Adaptor CIN85 Acts as an Inhibitory Binding Partner of Hypoxia-Inducible Factor Prolyl Hydroxylase 2

Nina Kozlova; Daniela Mennerich; Anatoly Samoylenko; Elitsa Y. Dimova; Peppi Koivunen; Ekaterina Biterova; Kati Richter; Antti Hassinen; Sakari Kellokumpu; Aki Manninen; ...
Open Access English
  • Published: 15 Aug 2019
  • Country: Finland
Abstract
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 in vivo, as specific loss of the CIN85-PHD2 interaction in CRISPR/Cas9-edited cells affected growth and migration properties,...
Subjects
free text keywords: CBL-INTERACTING PROTEIN, BREAST-CANCER, SH3 DOMAINS, PROLYL-4-HYDROXYLASE PHD2, DOWN-REGULATION, HIF-ALPHA, C-CBL, COMPLEX, HIF-1-ALPHA, GROWTH, 3122 Cancers, Cancer Research, Oncology, Hypoxia (medical), medicine.symptom, medicine, In vivo, Downregulation and upregulation, Molecular biology, Cell biology, HIF1A, CRISPR, business.industry, business, Growth factor, medicine.medical_treatment, Cancer, medicine.disease, Cas9
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publication . Article . Other literature type . 2019

The Pro-Oncogenic Adaptor CIN85 Acts as an Inhibitory Binding Partner of Hypoxia-Inducible Factor Prolyl Hydroxylase 2

Nina Kozlova; Daniela Mennerich; Anatoly Samoylenko; Elitsa Y. Dimova; Peppi Koivunen; Ekaterina Biterova; Kati Richter; Antti Hassinen; Sakari Kellokumpu; Aki Manninen; ...