title: Functions, divergence and clinical value of TAp73 isoforms in cancer.
abstract: The p73 gene encodes the tumour suppressive full-length TAp73 and N-terminal-truncated DNp73 isoforms that act as dominant negative inhibitors of TAp73. The overall effect of p73 in oncogenesis is thought to depend on the TAp73 to DNp73 isoforms' ratio. TAp73 isoforms include a number of C-terminal variants as a result of alternative splicing in 3'-end. TAp73 isoforms protect cells from oncogenic alterations in a multifaceted way since they are implicated in the suppression of all demonstrated hallmarks and enabling characteristics of cancer. Their best established role is in apoptosis, a process which seems to be differently affected by each TAp73 C-terminal variant. Based on previous findings and our thorough bioinformatics analysis, we highlight that TAp73 variants are functionally non-equivalent, since they present major differences in their transactivation efficiencies, protein interactions, response to DNA damage and apoptotic effects that are attributable to the primary structure of their C terminus. In this review, we summarise these differences and we unveil the link between crucial C-terminal motifs/residues and the oncosuppressive potential of TAp73 isoforms, emphasising on the importance of considering C terminus during the development of p73-based anticancer biologics.
authors.affiliation: Unit of Biomedical Applications, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vas. Constantinou Ave, 11635, Athens, Greece.
authors.forename: Stella
authors.initials: S
authors.lastname: Logotheti
authors.forename: Athanasia
authors.initials: A
authors.lastname: Pavlopoulou
authors.forename: Sotiris
authors.initials: S
authors.lastname: Galtsidis
authors.forename: Borek
authors.initials: B
authors.lastname: Vojtesek
authors.forename: Vassilis
authors.initials: V
authors.lastname: Zoumpourlis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins