Figure 1. Schematic representation of VEGF promoter regulation by p53 family members and their isoforms. We have shown that p53 can positively regulate VEGF expression during the initial phases of hypoxia by direct binding to conserved sites in the VEGF promoter.³ It remains to be determined if p73 and dNp63 can synergistically act with HIF-1α in positively regulating VEGF expression during hypoxia by directly binding to this conserved site. We have also demonstrated that p53 can indirectly repress VEGF expression during continued hypoxic challenge that is genetically dependent on the presence of p21.³ Here it remains to be determined whether p73 and TAp63’s negative effects on VEGF expression are dependent on a functional p21-E2F pathway.