NQO1 inhibits proteasome-mediated degradation of HIF-1α

• DOI: 10.1038/ncomms13593
• Publication Date: 2016-12-14T10:24:45Z
• Authors: Eun-Taex Oh; Jung-whan Kim; Joon Mee Kim; Soo Jung Kim; Jae-Seon Lee; Soon-Sun Hong; Justin Goodwin; Robin J. Ruthenborg; Myung Gu Jung; Hae-June Lee; Chul-Ho Lee; Eun Sung Park; Chulhee Kim; Heon Joo Park
• Keywords: 0301 basic medicine; Proteasome Endopeptidase Complex; Protein Stability; Science; Q; Breast Neoplasms; Hypoxia-Inducible Factor 1, alpha Subunit; Article; 3. Good health; Oxygen; 03 medical and health sciences; Cell Line, Tumor; Gene Knockdown Techniques; NAD(P)H Dehydrogenase (Quinone); Homeostasis; Humans; Colorectal Neoplasms

Abstract Overexpression of NQO1 is associated with poor prognosis in human cancers including breast, colon, cervix, lung and pancreas. Yet, the molecular mechanisms underlying pro-tumorigenic capacities have not been fully elucidated. Here we show a previously undescribed function for stabilizing HIF-1α, master transcription factor oxygen homeostasis that has implicated survival, proliferation malignant progression cancers. We demonstrate directly binds to oxygen-dependent domain HIF-1α inhibits proteasome-mediated degradation by preventing PHDs from interacting HIF-1α. knockdown colorectal breast cancer cell lines suppresses HIF-1 signalling tumour growth. Consistent this NQO1, high expression levels correlate increased patient survival. These results collectively reveal oxygen-sensing mechanism regulates stability