Redox state of tumor suppressor p53 regulates its sequence-specific DNA binding in DNA-damaged cells by cysteine 277.

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 Res

journal_title

Nucleic acids research

authors

Buzek J,Latonen L,Kurki S,Peltonen K,Laiho M

doi

10.1093/nar/30.11.2340

keywords:

subject

Has Abstract

pub_date

2002-06-01 00:00:00

pages

2340-8

issue

11

eissn

0305-1048

issn

1362-4962

journal_volume

30

pub_type

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