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Cancer Biol Ther. 2005 Apr;4(4):414-8. Epub 2005 Apr 21.

The tumor suppressor protein p53 functions similarly to p63 and p73 in activating transcription in vitro.

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  • 1Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachussetts 02115, USA.

Abstract

The p53 tumor suppressor protein functions via specific gene activation to inhibit passage through the cell cycle and to trigger apoptosis. The p53 protein is homologous to p63 and p73, proteins that regulate transcription via the same promoter sequences but which activate different genes. In this study we tested whether p53, p63, and p73 have different mechanisms of activating transcription and if such a difference could explain how each factor stimulates the transcription of distinct sets of genes. We found that when comparing p53 to the transcriptional activator, GAL4-VP16, both of which are classified as acidic activators, that stimulation of transcription by p53 is dependent upon low Mg2+ concentrations and limiting amounts of extract. By comparison, the stimulation of RNA synthesis by GAL4-VP16 was not dependent on a specific concentration of Mg2+ but did require higher amounts of extract, suggesting that a certain factor not required for p53-dependent gene activation was limiting in the extract. In contrast to the differences between p53 and GAL4-VP16, p63 and p73 both regulated transcription in vitro under similar conditions as did p53. All three proteins, purified to near homogeneity, were equally active in binding to the p53-response element, and equally active in stimulating transcription reactions using naked DNA templates, DNA templates reconstituted in chromatin using histones purified from HeLa cells, or hyper-acetylated histones. These results argue that the gene specificity of p63 and p73 dependent activation of transcription depends upon specific coactivators present in the specific cell types and upon other factors bound to the promoters.

PMID:
15846087
[PubMed - indexed for MEDLINE]
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