Oxygen-independent degradation of HIF- via bioengineered VHL tumour suppressor complex
Tumour hypoxia promotes the accumulation of the otherwise oxygen-labile hypoxia-inducible factor (HIF)- subunit whose expression is associated with cancer progression, poor prognosis and resistance to conventional radiation and chemotherapy. The oxygen-dependent degradation of HIF- is carried out by the von Hippel-Lindau (VHL) protein-containing E3 that directly binds and ubiquitylates HIF- for subsequent proteasomal destruction. Thus, the cellular proteins involved in the VHL-HIF pathway have been recognized as attractive molecular targets for cancer therapy. However, the various compounds designed to inhibit HIF- or HIF-downstream targets, although promising, have shown limited success in the clinic. In the present study, we describe the ...
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