Fig. 7. Schematic diagram of the proposed mechanism that represses the HIF-1α transactivation by pVHL and the VHLaK protein. Based on the data presented in this study and previously published findings, we propose that pVHL not only mediates the ubiquitylation and degradation of HIF-1α in the cytoplasm, but also recruits the VHLaK protein, through interaction with the KRAB-A domain, to HIF-1α transcription factor complex. The VHLaK protein forms homo-oligomerization via its SCAN domain and can recruit KAP-1/KRIP-1/TIF-1β, a well- characterized transcriptional repressor, to repress the transcriptional activity of HIF-1α.