A NOVEL PROTEIN COMPLEX INVOLVED IN SIGNAL-TRANSDUCTION POSSESSING SIMILARITIES TO 26S PROTEASOME SUBUNITS

A novel protein complex has been identified in human cells that has a molecular mass of approximately 450 kDa. It consists of at least eight different subunits including JAB1, the Jun activation-domain binding protein 1, and Trip15, the thyroid hormone receptor-interacting protei n 15. The purified complex contains COP9 and COP11 protein homologs an d is very similar, if not identical, to the plant COP9 complex involve d in light-mediated signal transduction. The isolated JAB1-containing particle has kinase activity that phosphorylates I kappa B alpha, the carboxy terminus of p105, and Ser(63) and/or Ser(73) of the amino-term inal activation domain of c-Jun. The phosphorylation of c-Jun requires the carboxy terminus of the protein containing the DNA binding and di merization domains. Three subunits of the new complex-Sgn3, Sgn5/JAB1, and Sgn6-exhibit sequence similarities to regulatory components of th e 26S proteasome, which could indicate the existence of common substra te binding sites. Immunofluorescence staining reveals that the new com plex shows a subcellular distribution similar to that of the 26S prote asome. The functional relationship of the two particles in regulating transcriptional activity is discussed. Considering the putative role o f the complex in signal transduction and its widespread occurrence,we suggest the name JAB1-containing signalosome.