| 摘要 |
<p>The present invention discloses that OS-9 interacts with both HIF-la and HIF-la prolyl hydroxylases. Overexpression of OS-9 promotes the hydroxylation of HIF-la, HIF-la binding to VHL, proteasomal degradation of HIF-la, and loss of HIF-1-mediated transcription. OS-9 loss-of-function increases HIF-la protein levels and HIF-1-mediated transcription under non-hypoxic conditions. These data indicate that OS-9 is an essential component of a multiprotein complex that regulates HIF-la protein levels in an O<SUB>2</SUB> dependent manner. Agents which modulate this complex, and methods to identify such agents, are disclosed.</p> |
