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 p21(WAF1/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.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Buzek J,Latonen L,Kurki S,Peltonen K,Laiho Mdoi
10.1093/nar/30.11.2340keywords:
subject
Has Abstractpub_date
2002-06-01 00:00:00pages
2340-8issue
11eissn
0305-1048issn
1362-4962journal_volume
30pub_type
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