DIFFERENTIAL INTERACTIONS OF REL-NF-KAPPA-B COMPLEXES WITH I-KAPPA-B-ALPHA DETERMINE POOLS OF CONSTITUTIVE AND INDUCIBLE NF-KAPPA-B ACTIVITY

The Rel-NF-kappa B family of transcription factors plays a crucial rol e in the regulation of genes involved in inflammatory and immune respo nses. We demonstrate that in vivo, in contrast to the other members of the family, RelB associates efficiently only with NF-kappa B1 (p105-p 50) and NF-kappa B2 (p100-p52), but not with cRel or p65. The RelB-p52 heterodimers display a much lower affinity for I kappa B alpha than R elB-p50 heterodimers or p65 complexes. However, similarly to the other Rel-NF-kappa B complexes, RelB-p52 can upregulate the synthesis of I kappa B alpha leading to the cytoplasmic trapping of dimers which have a higher affinity for the inhibitor. We suggest that a hierarchy of i nteractions between I kappa B alpha and the different Rel-NF-kappa B c omplexes governs their cellular distribution. This results in the pres ence of two distinct pools of NF-kappa B activity which differ in thei r composition: one a constitutive nuclear and the other an inducible c ytoplasmic activity.