It has been shown that the molecular mechanism by which cytokines and gluco
corticoids mutually antagonize their functions involves a mutual glucocorti
coid receptor (GR)/nuclear factor-kappaB (NF-kappaB) transrepression, Here
we report a role for the nuclear receptor coactivator RAC3, in modulating N
F-kappaB transactivation. We found that RAC3 functions as a coactivator by
binding to the active form of NF-kappaB and that overexpression of RAC3 res
tores GR-dependent transcription neglecting GR/NF-kappaB transrepression, T
he 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. Publ
ished by Elsevier Science B.V. All rights reserved.