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Identification of targets specifically regulated by a 'super hybrid p53'

ABSTRACT: p63, like its homologue, the tumor suppressor p53, is also able to induce apoptosis in several cancer cell types. p53 family proteins are composed of three characteristic domains which are: 1) an N-terminal transactivation domain (TAD); 2) a central DNA-binding domain (DBD); and 3) an oligomerization domain (OD). In this study, we constructed recombinant adenoviruses containing hybrid genes composed of fragments of p53 and TAp63γ genes by connecting coding sequences of their three functional domains. The potency of tumor growth suppression of these hybrid molecules was evaluated using in vitro and in vivo models. One of the p53-p63 hybrid molecules, p63-53O, was observed to be the most potent activator of human cancer cells to apoptosis when compared to the p53, TAp63γ or several alternative p53-p63 hybrid molecules. p63-53O hybrid is composed of TAD and DBD of TAp63γ and OD of p53. In an effort to identify specific targets regulated by pro-apoptotic hybrid p63-53O, we next performed Affymetrix Genechip analysis and compared expression patterns in a human osteosarcoma cell line Saos-2 transfected separately with Ad-p53, Ad-TAp63γ and Ad-p63-53O.

ORGANISM(S): Homo sapiens

PROVIDER: GSE35512 | GEO | 2012/02/04

SECONDARY ACCESSION(S): PRJNA152323

REPOSITORIES: GEO

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Identification of targets specifically regulated by a 'super hybrid p53'

Project description:p63, like its homologue, the tumor suppressor p53, is also able to induce apoptosis in several cancer cell types. p53 family proteins are composed of three characteristic domains which are: 1) an N-terminal transactivation domain (TAD); 2) a central DNA-binding domain (DBD); and 3) an oligomerization domain (OD). In this study, we constructed recombinant adenoviruses containing hybrid genes composed of fragments of p53 and TAp63γ genes by connecting coding sequences of their three functional domains. The potency of tumor growth suppression of these hybrid molecules was evaluated using in vitro and in vivo models. One of the p53-p63 hybrid molecules, p63-53O, was observed to be the most potent activator of human cancer cells to apoptosis when compared to the p53, TAp63γ or several alternative p53-p63 hybrid molecules. p63-53O hybrid is composed of TAD and DBD of TAp63γ and OD of p53. In an effort to identify specific targets regulated by pro-apoptotic hybrid p63-53O, we next performed Affymetrix Genechip analysis and compared expression patterns in a human osteosarcoma cell line Saos-2 transfected separately with Ad-p53, Ad-TAp63γ and Ad-p63-53O. Saos-2 osteosarcoma cells were either transduced with adenoviral vectors expressing p53, TAp63gamma, p53-p63 hybrid (p63-53O), or GFP. After 24 hours, mRNA was isolated and analyzed by hybridization to Affymetrix HG-U133 plus 2 arrays.

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