Estrogen receptor α is a novel target of the Von Hippel-Lindau protein and is responsible for the proliferation of VHL-deficient cells under hypoxic conditions.

ABSTRACT: The Von Hippel-Lindau gene (VHL) is frequently deleted or mutated in human renal cell carcinoma (RCC) at the early stage. According to the well-established theory, pVHL acts as a tumor suppressor through its E3 ligase activity, which targets hypoxia-inducing factor-1α (HIF-1α). However, the elevated expression of HIF-1α did not promote cell proliferation, indicating that there would be another target, which could promote cell proliferation at the early cancer stage of RCC. In this study, we show that estrogen receptor-α (ER-α) is a novel proteasomal degradation target of the pVHL E3 ligase. Indeed, the overexpression of VHL suppresses exo- and endogenous ER-α expression, whereas si-pVHL can increase ER-α expression. The negative regulation of pVHL on ER-α expression is achieved by its E3 l

SUBMITTER: Jung YS 

PROVIDER: S-EPMC3552928 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature