Redox state of tumor suppressor p53 regulates its sequence-specific DNA binding in DNA-damaged cells by cysteine 277 |
| |
| Authors: | Buzek Jiri Latonen Leena Kurki Sari Peltonen Karita Laiho Marikki |
| |
| Affiliation: | Department of Virology, Haartman Institute, and Molecular Cancer Biology Program, Biomedicum Helsinki, University of Helsinki and Helsinki University Central Hospital Laboratory Diagnostics, PO Box 63, FIN-00014 Helsinki, Finland. |
| |
| Abstract: | Using a bio-oligo pull-down DNA-binding assay we investigated the binding capacity of endogenous, DNA damage-induced p53 in human diploid fibroblasts to several p53-responsive elements (REs) present in p53-regulated genes. During the course of p53 accumulation, we observed a decrease in p53 binding to the GADD45 but not to the p21WAF1/CIP1 RE. Using mutated GADD45 sequences we show that this change is dependent on the presence of cytosines at position 3 in RE pentamers and on the p53 redox state. Site-directed mutagenesis experiments demonstrated that Cys277 (a residue directly contacting base 3 in a RE pentamer) is critical for differential regulation of GADD45 in DNA-damaged cells. These data represent a novel mechanism for differential affinity of p53 to distinct REs. |
| |
| Keywords: | |
| 本文献已被 PubMed 等数据库收录！ |
|
