The structure of NF-κB family proteins and their role in apoptosis

The NF-kappa B protein family encompasses transcription factors involved in controlling the expressions of genes which are crucial for several processes taking part at the cellular level. Five transcription factors, differing in the structure of the polypeptide chain of the C terminus, have been discovered in mammals so far. NF-kappa B heterodimers play a physiological role and their activity remains under strict control. The most common is a dimer composed of p50/RelA (p50/p65) proteins. NF-kappa B complexes are retained in the cytoplasm due to their interaction with kappa B inhibitors (I kappa B). When stimulated, I kappa B undergoes phosphorylation and then degradation in a proteasome, while the free NF-kappa B dimer is translocated to the cell nucleus, where it regulates the transcription of target genes. A key role in I kappa B phosphorylation is played by kinases of kappa B inhibitors (IKKs). They involve a protein complex encompassing two enzymatic subunits, IKK alpha and IKK beta, and the regulatory subunit NEMO. Three principal pathways of NF-kappa B activation are distinguished, which involve distinct NF-kappa B dimers. Activators of the classical triggering pathway include, among others, lipopolysaccharide composing the envelope of Gram-negative bacteria, viruses, and pro-inflammatory cytokines. Another activation pathway is induced by the action of such proteins as lymphotoxin beta. NF-kappa B transcription factor also becomes activated in response to DNA damage. As generally recognized, NF-kappa B exerts an anti-apoptotic action, promoting the survival of defective cells, which may result in the development of several tumors. Nevertheless, recent reports also point to a pro-apoptotic activity of NF-kappa B. This review is an attempt to present current knowledge on the involvement of NF-kappa B transcription factor in cell death by apoptosis.