Some damaged cells can be fixed, but others have to die. It has been a puzzle how the tumour suppressor p53 determines the cell's fate depending on the damage done. This week’s Nature (Vol. 422, No. 6931, pp. 527-531, 03 April 2003) reports that the phosphatase PAC1 is necessary and sufficient to induce p53-dependent cell death.
The tumour suppressor p53 coordinates various cellular processes by regulating the transcription of specific genes. Yuxin Yin of the College of Physicians and Surgeons, Columbia University, New York now show that the transcription of PAC1 — known to inactivate the MAP kinase cell-survival pathway — is directly regulated by p53.
PAC1 is activated only by stress that results in the cell's demise — for example, oxidative damage — and not in response to gamma-irradiation, which causes cell-cycle arrest. "This explains how p53 may suppress the MAP kinase pathway to kill cancer cells," the authors conclude.
Unexpectedly, p53 activates the transcription of PAC1 in a rather unusual manner: it binds a ‘palindromic’ site in the PAC1 promoter, rather than the ‘consensus’ p53-binding site.
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