Nikitovic D, Holmgren A, Spyrou G
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Sweden.
Biochem Biophys Res Commun. 1998 Jan 6;242(1):109-12. doi: 10.1006/bbrc.1997.7930.
Nitric oxide (NO), which has diverse biological effects, can modulate AP-1 activity. Since DNA binding of Jun-Jun and Jun-Fos dimers is regulated in vitro by redox control involving conserved cysteines, we hypothesized that the action of NO is mediated via these residues. We performed electrophoretic mobility-shift analyses using Jun and Fos recombinant proteins and NO solutions. Cysteine-to-serine mutants showed that the inhibition of AP-1 activity following NO treatment was dependent on the presence of Cys7272 and Cys154 in the DNA binding domain of Jun and Fos, respectively. The inhibitory effect of NO was reversed by DTT and the thioredoxin system. Our results demonstrate that NO mediates its inhibitory effect by reacting specifically with the conserved cysteine residues in Jun and Fos.
具有多种生物学效应的一氧化氮（NO）可调节AP-1活性。由于Jun-Jun和Jun-Fos二聚体的DNA结合在体外受涉及保守半胱氨酸的氧化还原控制调节，我们推测NO的作用是通过这些残基介导的。我们使用Jun和Fos重组蛋白以及NO溶液进行了电泳迁移率变动分析。半胱氨酸到丝氨酸突变体表明，NO处理后AP-1活性的抑制分别取决于Jun和Fos的DNA结合结构域中Cys7272和Cys154的存在。DTT和硫氧还蛋白系统可逆转NO的抑制作用。我们的结果表明，NO通过与Jun和Fos中保守的半胱氨酸残基特异性反应来介导其抑制作用。
