Multi-step activation of NF-kappa B/Rel transcription factors

Transcription factors belonging to the NF-kappa B/Rel family are specialized in the transduction of primarily pathogenic signals from the cytoplasm to the cell nucleus. To date, the family comprises five distinct DNA-binding subunits and five regulatory proteins with inhibitory function, called I kappa B proteins. The interaction of dimers of the DNA-binding subunits with the I kappa B proteins leads to the cytoplasmatic retention of the complex and inhibition of its DNA binding. Following stimulation of cells, the I kappa B proteins become phosphorylated and are subsequently degraded, presumably, by the proteasome. The released NF-kappa B/Rel transcription factors can then enter the nucleus, 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-kappa B/Rel transcription factors can be regulated.