Nina Kozlova, Daniela Mennerich, Anatoly Samoylenko, Elitsa Y Dimova, Peppi Koivunen, Ekaterina Biterova, Kati Richter, Antti Hassinen, Sakari Kellokumpu, Aki Manninen, Ilkka Miinalainen, Virpi Glumoff, Lloyd Ruddock, Lyudmyla Borysivna Drobot, Thomas Kietzmann
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...
August 15, 2019: Cancer Research