PAC-p53 interactions

The tumor suppressor protein p53 has a role in cellular apoptosis through the transcriptional regulation of several target genes, including PAC1 (phosphatase of activated cells 1) which inactivates mitogen-activated protein (MAP) kinases. However, the molecular mechanisms of interaction between p53 and PAC1 have been unclear. In the April 3 Nature, Yuxin Yin and colleagues at Columbia University, New York, show that under specific stress conditions, p53 regulates transcription of PAC1 through a novel p53-binding site, and that PAC1 is necessary and sufficient for p53-mediated apoptosis (Nature, 422:527-531, April 3, 2003).

Yin et al. used a p53-inducible system comprising EB-1 cells derived from a human colon cancer with mutant p53. They observed that PAC1 transcription was induced in these cells in response to serum deprivation and oxidative stress, resulting in p53-dependent apoptosis. Using small interfering RNA they reduced PAC1 transcription and observed an inhibition of p53-mediated apoptosis. Overexpression of PAC1 increased ...