NF-kB p105 / p50 Mouse Monoclonal Antibody [A2-7]

Function

NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators.

Background References

1. "Casper/c-FLIP is physically and functionally associated with NF-kappaB1 p105." Li Z., Zhang J., Chen D., Shu H.B. Biochem. Biophys. Res. Commun. 309:980-985(2003)

2. "Identification of a ZU5 and death domain-containing inhibitor of NF-kappaB." Zhang J., Xu L.-G., Han K.-J., Shu H.-B. J. Biol. Chem. 279:17819-17825(2004)

3. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome." Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H. J. Proteomics 96:253-262(2014)

Post-translational Modification

While translation occurs, the particular unfolded structure after the GRR repeat promotes the generation of p50 making it an acceptable substrate for the proteasome. This process is known as cotranslational processing. The processed form is active and the unprocessed form acts as an inhibitor (I kappa B-like), being able to form cytosolic complexes with NF-kappa B, trapping it in the cytoplasm. Complete folding of the region downstream of the GRR repeat precludes processing.; Phosphorylation at 'Ser-903' and 'Ser-907' primes p105 for proteolytic processing in response to TNF-alpha stimulation. Phosphorylation at 'Ser-927' and 'Ser-932' are required for BTRC/BTRCP-mediated proteolysis.; Polyubiquitination seems to allow p105 processing.; S-nitrosylation of Cys-61 affects DNA binding.; The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S-nitrosylation and S-palmitoylation.

Subcellular Location

Nucleus. Cytoplasm.

UNIPROT

SwissProt: P19838 Human

Synonyms