Previous studies showed that the binding of p50/NFkappaB1 to particular kappaB 
DNA sites altered its conformation in a way that correlated with transcriptional 
activation. Here, we investigated the effects of protein-protein interactions on 
the transcriptional activity of p50. We show that the association of p50 with a 
mutant Rel-homology domain (RHD) defective for DNA binding led to synergistic 
activation of kappaB site-dependent transcription, whereas neither protein alone 
had any effect. Partial proteolytic analysis showed that the conformation of p50 
in these complexes differed from that in wild-type c-Rel-RHD/p50 complexes, and 
correlated with activated transcription. These results suggest that the 
Rel-homology domain can act as an allosteric effector to promote transcription 
by p50/NFkappaB1 and that the configuration of p50 is important for its 
activity. This also suggests that Rel proteins can promote transcription by 
other Rel-family members without binding to their DNA recognition site. These 
studies emphasize the important role of protein-protein interactions in Rel and 
NFkappaB-mediated transcription.