| First Author | Ordway JM | Year | 2003 |
| Journal | Mol Cell Biol | Volume | 23 |
| Issue | 12 | Pages | 4257-66 |
| PubMed ID | 12773568 | Mgi Jnum | J:83750 |
| Mgi Id | MGI:2663388 | Doi | 10.1128/MCB.23.12.4257-4266.2003 |
| Citation | Ordway JM, et al. (2003) Cysteine 64 of Ref-1 is not essential for redox regulation of AP-1 DNA binding. Mol Cell Biol 23(12):4257-66 |
| abstractText | Ref-1 participates in DNA repair as well as in redox regulation of transcription factor function. The redox function of Ref-1 involves reduction of oxidized cysteine residues within the DNA binding domains of several transcription factors, including Fos and Jun. Reduction of these residues is required for DNA binding, providing a redox-dependent mechanism for regulation of target gene expression. Previous in vitro studies implicated cysteine 65 of human Ref-1 (cysteine 64 of mouse Ref-1) as the redox catalytic site. We analyzed the in vivo role of cysteine 64 in redox regulation of AP-1 activity by introducing a cysteine-to-alanine point mutation into the endogenous mouse Ref-1 gene (ref-1(C64A)). Unlike Ref-1 null mice, which die very early in embryonic development, homozygous ref-1(C64A) mice are viable, they survive to normal life expectancy, and they display no overt abnormal phenotype. Although Ref-1 provides the major AP-1-reducing activity in murine cells, ref-1(C64A) cells retain normal levels of endogenous AP-1 DNA binding activity in vivo as well as normal Fos- and Jun-reducing activity in vitro. These results demonstrate that Ref-1 cysteine 64/65 is not required for redox regulation of AP-1 DNA binding in vivo, and they challenge previous hypotheses regarding the mechanism by which Ref-1 regulates the redox-dependent activity of specific transcription factors. |
