A transcriptional activation function of p53 is dispensable for and inhibitory of its apoptotic function

Oncogene
J M KokontisN Hay

Abstract

The tumor suppressor p53 is an inducer of cell cycle arrest and programmed cell death (apoptosis). The ability of p53 to induce cell cycle arrest is linked to its ability to induce transcription of genes such as the cyclin-dependent kinase inhibitor p21. However, the dependence of p53-mediated apoptosis on transcriptional activation remains controversial. Ectopic expression of a temperature-sensitive (ts) p53 allele induced expression of p53 target genes and elicited both G1 and G2/M cell cycle arrest upon shift to the permissive temperature. Ectopic expression of the same ts p53 allele with two additional point mutations (Gln22, Ser23) that abolish p53-transcriptional activation did not induce p53 target genes and G1 nor G2/M cell cycle arrest. In HCT116 colon carcinoma cells ectopic expression of wild type p53 does not elicit apoptosis whereas p53 mutant deficient in trans-activation induces apoptosis. The ability of wild type p53 to induce apoptosis is restored in HCT116 cells that are null for p21. However, the trans-activation deficient mutant of p53 is still more potent mediator of apoptosis than wild type p53 in the p21 null cells. Although the ability of Gln22,Ser23 to trans-activate p53 target genes is diminished, it r...Continue Reading

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Citations

Jan 26, 2007·Apoptosis : an International Journal on Programmed Cell Death·M A Christine PrattMin Ying Niu
Apr 20, 2005·Brain Research. Molecular Brain Research·Xiaonan Zhu, Steven H Zeisel
Sep 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Zhuo ZhangRuiwen Zhang
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