TAX INDUCES NUCLEAR TRANSLOCATION OF NF-KAPPA-B THROUGH DISSOCIATION OF CYTOPLASMIC COMPLEXES CONTAINING P105 OR P100 BUT DOES NOT INDUCE DEGRADATION OF I-KAPPA-B-ALPHA MAD3/

The activity of the NF-kappa B transcription factor is controlled thro ugh cytoplasmic retention by either of two types of molecules: the inh ibitor I kappa B alpha/MAD3 or the p105 and p100 precursors of the p50 and p52 DNA-binding subunits. Treatment of cells with classical NF-ka ppa B inducers such as tumor necrosis factor, interleukin-1, phorbol m yristate acetate, and lipopolysaccharide results in MAD3 degradation f ollowed by nuclear translocation of NF-kappa B. On the other hand, the mechanisms involved in the dissociation of the cytoplasmic p105/p100 containing complexes are largely unknown. The Tax protein encoded by h uman T-cell leukemia virus type 1 is a potent activator of viral and c ellular gene transcription. It does not bind DNA directly but seems to activate transcription indirectly either by enhancing the activities of the transcription factors that recognize responsive elements locate d in the promoters of the Tax-responsive genes or by forming ternary c omplexes with these factors and DNA. It has been previously shown that Tax is able to induce nuclear translocation of NF-kappa B. We demonst rate here that Tax can induce translocation of members of the NF-kappa B family retained in the cytoplasm through their interaction with eit her p105 or p100. On the other hand, Tax induces no apparent degradati on of MAD3, although experiments using cycloheximide indicate that it decreases the half-life of MAD3. However, this activity is shared by a mutant of Tax which is unable to activate NF-kappa B. These results s uggest that Tax activates NF-kappa B essentially through the p105/p100 retention pathway.