Proteins, proteomics


NF-κB, Nuclear Factor kappa Bs, are ubiquitous transcription factors involved in responses to cellular stressors such as cytokines, free radicals, UV irradiation, bacterial antigens, and viral antigens.

action of IκB : actions of NF-κB : family : free NF-κB : IκB : IkappaBalpha : IκB kinase : IKK : NF-κB family : NF-κB/rel : tumors and NF-κB : v-Rel

Members of the NF-κB family are classified as NF-κB/Rel proteins because they display structural homology to the retroviral oncoprotein v-Rel, and include mammalian members:
● N-terminal homology with v-Rel
___ ● NF-κB1 (p50)
___ ● NF-κB2 (p52)
_plus trans-activation domain in C-termini
____ ● RelA (p65)
____ ● RelB
____ ● c-Rel

[] 3D transcription factor NFkappaB -helix-loop-helix []

NF-κB1 and NF-κB2 are synthesized as large precursors (p105, and p100) that undergo selective degradation of their C-terminal region by the ubiquitin/proteasome pathway to generate the mature NF-κB subunits ( p50, and p52 respectively). Degradation of p100 to p52 is tightly regulated process, whereas p50 is generated by constitutive processing of p105. RelA, RelB, and c-Rel contain trans-activation domains at their C-termini. (p52 is not to be confused with the tumor suppressor gene p53.)

Inhibitor of kappa B (IκB, IkappaBalpha) inactivates NF-κB by sequestering NF-κB dimers within the cytoplasm. Activation of IκB kinase (IKK) by stress signals stimulates phosphorylation of two serine residues in IκB's regulatory domain, targetting the IκB molecules for ubiquitin/proteasome degradation, and releasing NF-κB from inhibition.

Free NF-κB translocates to the nucleus where it binds to specific κB sequences in DNA, initiating transcription of related genes, including those for immunoreceptors, cytokines, and its own inhibitor, IκB. Physiological activities mediated by NF-κB include cellular proliferation, and inflammatory, immune, and cellular survival responses. [] signaling pathways []

Many tumor types have chronically active, dysregulated NF-κB, resulting from:
mutations in genes encoding the NF-κB transcription factors themselves, or
mutations in genes that control NF-κB activity


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. . . since 11/21/06