title: Mutation of a phosphorylation site in the DNA-binding domain is required for redox-independent transactivation of AP1-dependent genes by v-Jun.
abstract: The ability of the nuclear oncoprotein Jun to activate transcription is controlled both by level of DNA binding and by the activity of its transactivation domain. Control of DNA binding is achieved by two mechanisms: phosphorylation and redox regulation. Mutation of Ser-226 inhibits phosphorylation of the DNA binding, resulting in enhanced DNA-binding 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 activation of transcription. However, transactivation by c-Jun-Cys-252 is fully restored upon mutation of Ser-226. Both mutations are also found in the oncogenic counterpart of c-Jun, v-Jun, and are the only differences between these proteins in the DNA-binding domain, suggesting that v-Jun escapes down-modulation of DNA binding by both mechanisms. However, 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.
authors: Kernforschungszentrum Karlsruhe, Institut für Genetik, Germany.
authors: T
authors: T
authors: Oehler
authors: A
authors: A
authors: Pintzas
authors: S
authors: S
authors: Stumm
authors: A
authors: A
authors: Darling
authors: D
authors: D
authors: Gillespie
authors: P
authors: P
authors: Angel
mesh_terms: D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D016759:Oncogene Protein p65(gag-jun) / Q000502:physiology*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation
chemical_list: D016759:Oncogene Protein p65(gag-jun); D016755:Proto-Oncogene Proteins c-jun; D004247:DNA