Zheng, H. W., You, H., Zhou, X. Z., Murray, S. A., Uchida, T., Wulf, G., Gu, L., Tang, X. R., Lu, K. P., Xiao, Z. X. J. (October 2002) The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response. Nature, 419 (6909). pp. 849-853. ISSN 0028-0836
Abstract
p53 is activated in response to various genotoxic stresses resulting in cell cycle arrest or apoptosis(1,2). It is well documented that DNA damage leads to phosphorylation and activation of p53 (refs 1-3), yet how p53 is activated is still not fully understood. Here we report that DNA damage specifically induces p53 phosphorylation on Ser/Thr-Pro motifs, which facilitates its interaction with Pin1, a member of peptidyl-prolyl isomerase(4-9). Furthermore, the interaction of Pin1 with p53 is dependent on the phosphorylation that is induced by DNA damage. Consequently, Pin1 stimulates the DNA-binding activity and transactivation function of p53. The Pin1-mediated p53 activation requires the WW domain, a phosphorylated Ser/Thr-Pro motif interaction module, and the isomerase activity of Pin1. Moreover, Pin1-deficient cells are defective in p53 activation and timely accumulation of p53 protein, and exhibit an impaired checkpoint control in response to DNA damage. Together, these data suggest a mechanism for p53 regulation in cellular response to genotoxic stress.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | DEPENDENT PROLINE ISOMERIZATION CELL-CYCLE PHOSPHORYLATION MITOSIS PROTEIN MECHANISM BINDING KINASES STRESS JUN Multidisciplinary Sciences |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53 bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > phosphorylation |
| CSHL Authors: | |
| Communities: | CSHL labs > Zheng lab |
| Depositing User: | Matt Covey |
| Date: | October 2002 |
| Date Deposited: | 22 Aug 2014 16:04 |
| Last Modified: | 22 Aug 2014 16:04 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/30713 |
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