2 DISTINCT MECHANISMS CONTRIBUTE TO THE CONSTITUTIVE ACTIVATION OF RELB IN LYMPHOID-CELLS

The kappa B-motif is an important regulatory element both for constitu tive lymphoid-specific as well as ubiquitous inducible transcriptional activity. We have shown previously that different members of the NF-k appa B/Rel family of transcription factors are responsible for these d istinct functions. Whereas the p65/RelA protein is involved in inducib le kappa B-dependent transcription, RelB is associated with constituti ve activity in lymphoid cells. Here we have addressed the question of how RelB is constitutively activated in lymphoid cells. We demonstrate that this is achieved by two different mechanisms. Expression of relB as determined by measurement of stable RNA and protein levels is sign ificantly enhanced in lymphoid organs compared with non-lymphoid organ s. However, these observed differences in absolute amounts of RNA and protein would not suffice to explain the dramatic differences that are apparent at the level of active DNA binding complexes in extracts fro m the respective organs. We have therefore analyzed the interaction of RelB complexes with the I kappa B-alpha inhibitor protein. Our result s show that RelB-containing complexes present in lymphoid extracts are much less susceptible to inhibition by I kappa B-alpha than RelA- or RelB-containing complexes from non-lymphoid cells. This difference mig ht be due to post-translational modifications of the RelB protein or i nteraction with a lymphoid-specific cofactor for RelB.