title: p73: a Positive or Negative Regulator of Angiogenesis, or Both?
abstract: 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.
authors.affiliation: Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Singapore, Republic of Singapore; Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Republic of Singapore; Institute of Molecular and Cell Biology, Biopolis, Singapore, Republic of Singapore; Department of Biochemistry, National University of Singapore, Singapore, Republic of Singapore cmrksb@nccs.com.sg.
authors.forename: Kanaga
authors.initials: K
authors.lastname: Sabapathy
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A