Daniel E Foxler, Katherine S Bridge, John G Foster, Paul Grevitt, Sean Curry, Kunal M Shah, Kathryn M Davidson, Ai Nagano, Emanuela Gadaleta, Hefin I Rhys, Paul T Kennedy, Miguel A Hermida, Ting-Yu Chang, Peter E Shaw, Louise E Reynolds, Tristan R McKay, Hsei-Wei Wang, Paulo S Ribeiro, Michael J Plevin, Dimitris Lagos, Nicholas R Lemoine, Prabhakar Rajan, Trevor A Graham, Claude Chelala, Kairbaan M Hodivala-Dilke, Ian Spendlove, Tyson V Sharp
The adaptive cellular response to low oxygen tensions is mediated by the hypoxia-inducible factors (HIFs), a family of heterodimeric transcription factors composed of HIF-α and HIF-β subunits. Prolonged HIF expression is a key contributor to cellular transformation, tumorigenesis and metastasis. As such, HIF degradation under hypoxic conditions is an essential homeostatic and tumour-suppressive mechanism. LIMD1 complexes with PHD2 and VHL in physiological oxygen levels (normoxia) to facilitate proteasomal degradation of the HIF-α subunit...
August 2018: EMBO Molecular Medicine