ACTIVATION OF THE SERUM RESPONSE FACTOR BY P65 NF-KAPPA-B/

This study demonstrates that the NF-kappa B subunit p65 can act like a n accessory protein for the serum response factor (SRF) in transfectio n assays. p65 functionally synergizes with SRF to activate the transcr iption of a reporter construct dependent only on the serum response el ement (SRE). The synergy of the two factors requires neither a kappa B motif nor direct contact of p65 with DNA. Consistent with these resul ts, a physical complex containing p65 and SRF is observed in vitro. Sy nergy of the factors is independent of the previously described activa tion domains present on p65, ruling out indirect effects of p65, but s ynergy is dependent on the activation domain of SRF. The complexing of p65 and SRF is mediated by a segment of the SRF DNA binding domain, a region of the protein which has also been reported to inhibit its own activation domain. We speculate that p65, upon direct or facilitated interaction with SRF, may relieve the inhibitory activity of this segm ent, thus enabling the activation domain of SRF to become fully functi onal. In contrast to p65, the p50 subunit of NF-kappa B does not inter act significantly with SRF, either functionally or physically. The dat a suggest the intriguing possibility that NF-kappa B may participate i n the regulation of SRE-dependent promoters, expanding the range of ac tivities of this rapidly activatable transcription factor.