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Binding and regulation of HIF-1alpha by a subunit of the proteasome complex, PSMA7
1Center for Cellular Switch Protein Structure, Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon, South Korea. scho@mail.kribb.re.kr
Abstract:
The hypoxia-inducible factor-1alpha (HIF-1alpha) 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-1alpha regulation. PSMA7 was found to interact specifically with two subdomains of HIF-1alpha. PSMA7 inhibited the transactivation function of HIF-1alpha under both normoxic and hypoxia-mimicking conditions. In addition, we show that the PSMA7-mediated regulation of HIF-1alpha activity is associated with the proteasome pathway.