RAC-3 is a NF-kappa B coactivator.
It has been shown that the molecular mechanism by which cytokines and glucocorticoids mutually antagonize their functions involves a mutual glucocorticoid receptor (GR)/nuclear factor-kappa B (NF-kappa B) transrepression. Here we report a role for the nuclear receptor coactivator RAC3, in modulating NF-kappa B transactivation. We found that RAC3 functions as a coactivator by binding to the active form of NF-kappa B and that overexpression of RAC3 restores GR-dependent transcription neglecting GR/NF-kappa B transrepression. The competition between GR and NF-kappa B for binding to RAC3 may represent a general mechanism by which both transcription factors mutually antagonize their activity.
Werbajh
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Deparmento de Cs. Biológicas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, Argentina.
Nojek
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Lanz
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Costas
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D001667:Binding, Competitive; D005938:Glucocorticoids / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007163:Immunosorbent Techniques; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism*; D056921:Nuclear Receptor Coactivator 3; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D020218:Response Elements; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051996:Transcription Factor RelA; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D005938:Glucocorticoids; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D015534:Trans-Activators; D051996:Transcription Factor RelA; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D056921:Nuclear Receptor Coactivator 3