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Differential effects of diverse p53 isoforms on TAp73 transcriptional activity and apoptosis

Zorić, Arijana; Horvat, Anđela; Slade, Neda (2013) Differential effects of diverse p53 isoforms on TAp73 transcriptional activity and apoptosis. Carcinogenesis, 34 (3). pp. 522-529. ISSN 0143-3334

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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, while only Δ133p53α/β/γ isoforms 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, while Δ133p53α and β inhibit its apoptotic activity most efficiently. We have determined the half-life of different p53 isoforms: p53γ isoform has the shortest while 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 Δ40p53) 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.

Item Type: Article
Uncontrolled Keywords: p73; p53 isoforms; transactivation; apoptosis; protein-protein interaction
Divisions: Division of Molecular Medicine
Project titleProject leaderProject codeProject type
Uloga mreže proteina p53/p73 u sarkomima mekih tkiva čovjeka-Neda Slade098-0982464-2391MZOS
Depositing User: Arijana Zorić
Date Deposited: 12 Dec 2016 16:17
DOI: 10.1093/carcin/bgs370

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