Binding and regulation of HIF-1α by a subunit of the proteasome complex, PSMA7

Abstract

The hypoxia-inducible factor-1α (HIF-1α) is an important transcription factor for cellular responses to oxygen tension. It is rapidly degraded under normoxic conditions by the ubiquitin-dependent proteasome pathway. Here we report a critical role of the 20S proteasome subunit PSMA7 in HIF-1α regulation. PSMA7 was found to interact specifically with two subdomains of HIF-1α. PSMA7 inhibited the transactivation function of HIF-1α under both normoxic and hypoxia-mimicking conditions. In addition, we show that the PSMA7-mediated regulation of HIF-1α activity is associated with the proteasome pathway.