Figure 6.

Schematic representation of phosphorylation-dependent targeting of CREB to proteasomal degradation by hypoxia. Hypoxia elicits the rapid depletion of PP1, resulting in decreased dephosphorylation of proteins within the targeting sequence. Resultant hyperphosphorylation of proteins attracts ubiquitination (Ub) through the coordinated activities of E1, E2, and E3. Ubiquitination of targeted peptides leads to degradation via the 26S proteasome. Proteins degraded through this targeting system in hypoxia include transcriptional modulators important in transformation to the hypoxic phenotype.