ΔNp73 enhances HIF-1α protein stability through repression of the ECV complex.

ABSTRACT: Cellular responses to low oxygen conditions are mainly regulated by the Hypoxia-inducible factors (HIFs). Induction of HIF-1α in tumor cells activates the angiogenic switch and allows for metabolic adaptations. HIF-1α protein levels are tightly regulated through ubiquitin-mediated proteosomal degradation; however, high levels of HIF-1α is a common feature in many solid tumors and is thought to enhance cancer cell proliferation, migration, and survival. Here, we report that the oncogenic p73 isoform, ∆Np73, increases HIF-1α protein stability. We found that ∆Np73 represses expression of genes encoding subunits of the ECV complex, in particular Elongin C, Elongin B, Cullin 2, and Rbx1. The ECV complex is an E3 ligase complex responsible for polyubiquitinating HIF-1α. Loss of ∆Np73 increases u

SUBMITTER: Stantic M 

PROVIDER: S-EPMC6033838 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature