NFKB1

NFKB1 Background

Nuclear factor NF-kappa-B p105 subunit is a protein in humans that is encoded by the NFKB1 gene ^[1]. 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 ^[2]. 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 ^[3][4]. 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 ^[3]. The NFKB1/p105 pathway involves the unprocessed NFKB1/p105 which preferentially binds to a homodimer of processed NFKB1/p50 ^[4]. The complex is inactive, and ubiquitinylation of p105 followed by destruction is required for the liberation of the processed NFKB dimer ^[5]. The importance of the NFKB1 function can be seen in mouse models, where NFKB1-null mice display increased inflammation and susceptibility to certain forms of DNA damage, leading to cancer, and a rapid aging phenotype ^[6].

[1] Meyer R, Hatada EN, et al. Cloning of the DNA-binding subunit of human nuclear factor kappa B: the level of its mRNA is strongly regulated by phorbol ester or tumor necrosis factor alpha [J]. Proc Natl Acad Sci U S A. 1991, 88 (3): 966–70.
[2] Perkins ND. Integrating cell‐signalling pathways with NF‐κB and IKK function. Nat Rev Mol Cell Biol 2007, 8, 49–62.
[3] Moynagh PN. The NF‐κB pathway. J Cell Sci 2005, 118, 4589–4592.
[4] Barkett M and Gilmore TD. Control of apoptosis by Rel/NF-kappaB transcription factors. Oncogene. 18:6910–6924. 1999.
[5] Kravtsova-Ivantsiv Y, Shomer I, et al. KPC1-mediated ubiquitination and proteasomal processing of NF-jB1 p105 to p50 restricts tumor growth. Cell 2015, 161, 333–347.
[6] Tyrell Cartwright, Neil D. Perkins, et al. NFKB1: a suppressor of inflammation, ageing and cancer [J]. FEBS Journal 283 (2016) 1812–1822.