RAC-3 is a NF-κB 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-kappaB (NF-kappaB) transrepression, Here we report a role for the nuclear receptor coactivator RAC3, in modulating NF-kappaB transactivation. We found that RAC3 functions as a coactivator by binding to the active form of NF-kappaB and that overexpression of RAC3 restores GR-dependent transcription neglecting GR/NF-kappaB transrepression, The competition between GR and NF-kappaB for binding to RAC3 may represent a general mechanism by which both transcription factors mutually antagonize their activity. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.