[The structure of NF- kappaB family proteins and their role in apoptosis].
The NF-kappaB 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-kappaB 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-kappaB complexes are retained in the cytoplasm due to their interaction with kappaB inhibitors (IkappaB). When stimulated, IkappaB undergoes phosphorylation and then degradation in a proteasome, while the free NF-kappaB dimer is translocated to the cell nucleus, where it regulates the transcription of target genes. A key role in IkappaB phosphorylation is played by kinases of kappaB inhibitors (IKKs). They involve a protein complex encompassing two enzymatic subunits, IKKalpha and IKKbeta, and the regulatory subunit NEMO. Three principal pathways of NF-kappaB activation are distinguished, which involve distinct NF-kappaB 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-kappaB transcription factor also becomes activated in response to DNA damage. As generally recognized, NF-kappaB 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-kappaB. This review is an attempt to present current knowledge on the involvement of NF-kappaB transcription factor in cell death by apoptosis.
Piotrowska
Aleksandra
A
Katedra i Zakład Histologii i Embriologii Akademii Medycznej we Wrocławiu. ola@hist.am.wroc.pl
Izykowska
Ilona
I
Podhorska-Okołów
Marzena
M
Zabel
Maciej
M
Dziegiel
Piotr
P
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015870:Gene Expression; D016328:NF-kappa B / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
D016328:NF-kappa B