Figure 1.

Model for regulation of HIF1α by the cell cycle. Prior to G₁ phase, CDK1 is activated by binding to its CCNB/cyclin B partner. This leads to a block in lysosomal degradation of HIF1α and increased HIF-1 target gene expression and inhibition of DNA replication. During the G₁/S phase transition and during S phase, CDK2 activity mediated by binding to either CCNE/cyclin E or CCNA leads to an increase in lysosomal degradation of HIF1α allowing DNA replication to proceed. In cancer cell lines, CDK2 activity leads to a concurrent upregulation of HIF-1 transcriptional activity and target gene expression.