Fig. 1. Oxygen-dependent polyubiquitination of HIF by pVHL. The subunits of the heterodimeric transcription factor HIF contain a conserved proline residue (P) that becomes hydroxylated in the presence of oxygen. This serves as a signal for binding to the pVHL, which is a component of an E3 ubiquitin ligase containing elongin B (B), elongin C (C), Cul2, Rbx1, and an as yet identified ubiquitin conjugating enzyme (E2?).