title: Differential effects of diverse p53 isoforms on TAp73 transcriptional activity and apoptosis.
abstract: The p53 activities are due, at least in part, to its ability to form oligomers that bind to specific DNA sequences and activate transcription. Since some mutant p53 proteins and ΔNp73 isoforms form heterocomplexes with TAp73, we asked whether p53 isoforms can do the same and potentially act as dominant-negative inhibitors of TAp73. Moreover, it has already been found that some isoforms form complex with wtp53 and some of them inhibit p53 tumor-suppressor functions. Therefore, we studied the complex formation and co-immunoprecipitation assays show that all six p53 isoforms examined can form complexes with TAp73β, whereas only Δ133p53α/β/γ isoforms form complex with TAp73α. All p53 isoforms counteract TAp73β transactivation function but with different efficiency and in a promoter-dependent manner. Furthermore, apoptotic activity of TAp73β was augmented by coexpression of p53β, whereas Δ133p53α and β inhibit its apoptotic activity most efficiently. We have determined the half-life of different p53 isoforms: p53γ isoform has the shortest half-life, whereas Δ133p53γ has the longest half-life. Inhibitory interactions of two proteins in complex often lead to their stabilization. However, only three isoforms (Δ133p53α, Δ133p53β and Δ40p53α) stabilize TAp73β. We are convinced that defining the interactions between p53/p73 would give a new insight into how the p53 isoforms modulate the p73 functions in tumorigenesis.
authors.affiliation: Division of Molecular Medicine, Rudjer Bošković Institute, Bijenička 54,  10000 Zagreb, Croatia.
authors.forename: Arijana
authors.initials: A
authors.lastname: Zorić
authors.forename: Andela
authors.initials: A
authors.lastname: Horvat
authors.forename: Neda
authors.initials: N
authors.lastname: Slade
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006207:Half-Life; D006801:Humans; D049410:Luciferases, Renilla / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D055550:Protein Stability; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C495901:TP53 protein, human; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human; D049410:Luciferases, Renilla