MUTATION OF A PHOSPHORYLATION SITE IN THE DNA-BINDING DOMAIN IS REQUIRED FOR REDOX-INDEPENDENT TRANSACTIVATION OF AP1-DEPENDENT GENES BY V-JUN

The ability of the nuclear onocprotein Jun to activate transcription i s controlled both by level of DNA binding and by the activity of its t ransactivation domain. Control of DNA binding is achieved by two mecha nisms: phosphorylation and redox regulation. Mutation of Ser-226 inhib its phosphorylation of the DNA binding, resulting in enhanced DNA-bind ing and transactivation activity of Jun. In contrast, mutation of Cys- 252, which is the target for repression of DNA-binding activity under oxidative conditions, results in a strong decrease of Jun-specific act ivation of transcription. However, transactivation by c-Jun-Cys-252 is fully restored upon mutation of Ser-226. Both mutations are also foun d in the oncogenic counterpart of c-Jun, v-Jun, and are the only diffe rences between these proteins in the DNA-binding domain, suggesting th at v-Jun escapes down-modulation of DNA binding by both mechanisms. Ho wever, inhibition of phosphorylation of Ser-226 is absolutely required for the ability of v-Jun to activate transcription of AP-1-dependent genes in a redox-independent manner.