p73: a Positive or Negative Regulator of Angiogenesis,or Both?

The role of p73, the homologue of the tumor suppressor p53, in regulating angiogenesis has recently been extensively investigated, resulting in the publication of five articles. Of these, two studies suggested a suppressive role, while the others implied a stimulatory role for the p73 isoforms in regulating angiogenesis. A negative role for TAp73, the full-length form that is often associated with tumor suppression, in blood vessel formation, is consistent with its general attributes and was proposed to be effected indirectly through the degradation of hypoxia-inducible factor 1α (HIF1-α), the master angiogenic regulator. In contrast, a positive role for TAp73 coincides with its recently understood role in supporting cellular survival and thus tumorigenesis, consistent with TAp73 being not-mutated but rather often overexpressed in clinical contexts. In the latter case, TAp73 expression was induced by hypoxia via HIF1-α, and it appears to directly promote angiogenic target gene activation and blood vessel formation independent of HIF1-α. This mini review will provide an overview of these seemingly opposite recent findings as well as earlier data, which collectively establish the definite possibility that TAp73 is indeed capable of both promoting and inhibiting angiogenesis, depending on the cellular context.