NF-kB
Nuclear factor kB (NF-kB) is a nuclear transcription factor that regulates expression of a large number of genes that are critical for the regulation of apoptosis, viral replication, tumorigenesis, inflammation, and various autoimmune diseases. Composed of homo- and heterodimers of five members of the Rel family including NF-kB1(p50), NF-kB2 (p52), RelA, RelB, and c-Rel (Rel), activation of NF-kB is thought to be part of a stress response as it is activated by a variety of stimuli including growth factors, cytokines, lymphokines, UV, pharmacological agents, and stress. In its inactive form, NF-kB is sequestered in the cytoplasm, bound by members of the IkB family of inhibitor proteins, which include IkBa, IkBb, IkBg, and IkBe. The various stimuli that activate NF-kB cause phosphorylation of IkB (through the IkB kinase complex consisting of at least three proteins: IKK1/a, IKK2/b and IKK3/g), which is followed by its ubiquitination and subsequent degradation. This results in the exposure of the nuclear localization signals (NLS) on NF-kB subunits and the subsequent translocation of the molecule to the nucleus. In the nucleus, NF-kB binds with the consensus sequence (5’GGGACTTTCC-3’) of various genes, activating their transcription.
The study of NF-kB activation has never been more important than today. As its role in diverse biological processes, such as arthritis, asthma, heart disease, chronic inflammation, cancer and certain neuro-degenerative disorders, become clear, it is becoming apparent that more tools using evolving technology are needed. IMGENEX offers a broad portfolio of different NF-kB detection tools and technologies for measurement, quantitation, and elucidation of critical pathway components. These tools include both phospho and pan-specific mono- and polyclonal antibodies, novel non-radiometric readout assays for the quantification of IkBa phosphorylation levels and NF-kB/p65, as well as peptide decoy inhibitors. Also available is our expanding line of validated plasmid-based and synthetic RNA interference kits targeting specific NF-kB related proteins.
NF-kB dimers are sequestered in the cytosol of unstimulated cells via non-covalent interactions with a class of inhibitor proteins, called IkBs. To date seven IkBs have been identified: IkB-alpha, IkB-beta, IkB-gamma, IkB-epsilon, BCL3, p100 and p105. All known IkBs contain multiple copies of a 30-33 aa sequence, called ankyrin repeats which mediate the association between IkB and NF-kB dimers. The ankyrin repeats interact with a region in the RHD of the
NF-kB proteins and by this mask their NLS and prevent nuclear translocation. Signals that induce NF-kB activity cause the phosphorylation of IkBs, their dissociation and subsequent degradation, thereby allowing activation of the NF-kB complex. Activated NF-kB complex translocates into the nucleus and binds DNA at kB-binding motifs such as 5-prime GGGRNNYYCC 3-prime or 5-prime HGGARNYYCC 3-prime (where H is A, C, or T; R is an A or G purine; and Y
is a C or T pyrimidine) and induce gene expression. The degradation of IkB proteins that permits NF-KappaB molecules to move into the nucleus is also carried out by the proteasome but only after prior phosphorylation of IkB by the IKK (IkB Kinase Complex). The IKK is composed of three subunits: two, IKK-alpha (IKK1) and IKK-beta (IKK2), are bonafi de kinases, while the third, IKK-gamma (NEMO), has no catalytic activity but plays a critical regulatory role. IKK-alpha is the predominant IkB kinase. Phosphorylated IkB is recognized by Beta-TrCP, a component of the SCF (skp-1/Cul/F box) ubiquitin ligase complex that mediates poly-ubiquitination of IkB and its subsequent proteasomal degradation. In contrast, IKK-alpha mediates the phosphorylationdependent
processing of p100, resulting in the generation of p52.
NF-kB Pathway Inhibitory Peptides
| Cat. No.: | Description | |
|---|---|---|
| IMG-2000 | IKKy NEMO Binding Domain (NBD) Inhibitory Peptide Set | Functions as an IKKa/IKKb decoy by binding to IKKy NBD, thereby preventing formation of the IKK complex. |
| IMG-2001 | NF-kB p65 (Ser276) Inhibitory Peptide Set | Functions as a p65 decoy through phosphorylation of the Ser276 site on the peptide. |
| IMG-2002 | TRAF6 Inhibitory Peptide Set | Functions as a TRAF6 decoy by binding to the T6DP motif of RANK, thereby preventing binding of RANK to TRAF6. |
| IMG-2003 | NF-kB p65 (Ser529/536) Inhibitory Peptide Set | Functions as a p65 decoy through phosphorylation of the Ser529/536 sites on the peptide. |
| IMG-2004 | NF-kB p50 (NLS) Inhibitory Peptide Set | Functions as a p50 decoy by blocking the intracellular recognition mechanism of p50 NLS. |
| IMG-2005 | MyD88 Homodimerization Inhibitory Peptide Set | Functions as a decoy by binding to the MyD88 TIR domain. |
| IMG-2006 | TIRAP Inhibitory Peptide Set | Functions as a TIRAP decoy by binding to TIR interacting domains on specific TLR receptors. |
