| 摘要 |
The present invention discloses that OS-9 interacts with both HIF-1alpha and HIF-1alpha prolyl hydroxylases. Overexpression of OS-9 promotes the hydroxylation of HIF-1alpha, HIF-1alpha binding to VHL, proteasomal degradation of HIF-1alpha, and loss of HIF-1-mediated transcription. OS-9 loss-of-function increases HIF-1alpha 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-1alpha protein levels in an O2 dependent manner. Agents which modulate this complex, and methods to identify such agents, are disclosed.
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