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Title 

NQO1 inhibits proteasome-mediated degradation of HIF-1α

Authors 

E T OhJ W KimJ M KimS J KimJ S LeeS S HongJ GoodwinR J RuthenborgM G JungH J LeeChul Ho LeeE S ParkC KimH J Park

Publisher 

Nature Publishing Group

Issue Date 

2016

Citation 

Nature Communications, vol. 7, no. 0, pp. 13593-13593

Abstract 

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

ISSN 

2041-1723

Link 

http://dx.doi.org/10.1038/ncomms13593

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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