title: Targeting p73 in cancer.
abstract: p73 is a member of the p53 family of tumor suppressors. Transactivating isoforms of p73 (TAp73) have p53-like, anti-proliferative and pro-apoptotic activities that are crucial for an efficient chemotherapy response. In line with this, genetic studies in mice have confirmed that TAp73 acts as a tumor suppressor. However, in contrast to p53, which is commonly inactivated in human cancer by point mutations, the TP73 gene is almost never mutated. Instead, the tumor suppressor activity of TAp73 is inhibited through a variety of mechanisms including epigenetic silencing and complex formation with inhibitory proteins. All these mechanisms have in common that they are in principle reversible and therefore amenable to therapeutic intervention. Here, we will review how tumor cells control the tumor suppressor activity of TAp73 and discuss possible strategies targeting p73 for reactivation.
authors: Molecular Oncology, Department of Hematology, Oncology and Immunology, Institute of Molecular Biology and Tumor Research, Philipps-University Marburg, Marburg, Germany.
authors: Anna-Maria
authors: AM
authors: Maas
authors: Anne Catherine
authors: AC
authors: Bretz
authors: Elisabeth
authors: E
authors: Mack
authors: Thorsten
authors: T
authors: Stiewe
mesh_terms: D000818:Animals; D004249:DNA Damage; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016158:Genes, p53; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases