MULTISTEP ACTIVATION OF NF-CHI-B REL TRANSCRIPTION FACTORS/

Transcription factors belonging to the NF-aleph B/Rel family are speci alized in the transduction of primarily pathogenic signals from the cy toplasm to the cell nucleus. To date, the family comprises five distin ct DNA-binding subunits and five regulatory proteins with inhibitory f unction, called I aleph B proteins. The interaction of dimers of the D NA-binding sub-units with the I aleph B proteins leads to the cytoplas matic retention of the complex and inhibition of its DNA binding. Foll owing stimulation of cells, the I aleph B proteins become phosphorylat ed and are subsequently degraded, presumably, by the proteasome. The r eleased NF-aleph B/Rel transcription factors can then enter the nucleu s, bind to decameric DNA cognate sequences and stimulate transcription of numerous immunologically important target genes. In this article, we discuss several distinct levels at which the NF-aleph B/Rel transcr iption factors can be regulated.