NFKB1 (MIM 164011) or NFKB2 (MIM 164012) is bound to REL (MIM 164910), RELA (MIM 164014), or RELB (MIM 604758) to form the NFKB complex. The NFKB complex is inhibited by I-kappa-B proteins (NFKBIA, MIM 164008, or NFKBIB), which inactivate NF-kappa-B by trapping it in the cytoplasm. Phosphorylation of serine residues on the I-kappa-B proteins by kinases (IKBKA, MIM 600664 or IKBKB, MIM 603258) marks them for destruction via the ubiquitination pathway, thereby allowing activation of the NF-kappa-B complex. Activated NFKB complex translocates into the nucleus and binds DNA at kappa-B-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).[supplied by OMIM][2]
↑Okamoto T, Ono T, Hori M, Yang JP, Tetsuka T, Kawabe T, Sonta S (November 1998). "Assignment of the IkappaB-beta gene NFKBIB to human chromosome band 19q13.1 by in situ hybridization". Cytogenet Cell Genet. 82 (1–2): 105–6. doi:10.1159/000015077. PMID9763672.
↑Woronicz JD, Gao X, Cao Z, Rothe M, Goeddel DV (October 1997). "IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK". Science. 278 (5339): 866–9. doi:10.1126/science.278.5339.866. PMID9346485.
↑Chen Y, Wu J, Ghosh G (June 2003). "KappaB-Ras binds to the unique insert within the ankyrin repeat domain of IkappaBbeta and regulates cytoplasmic retention of IkappaBbeta x NF-kappaB complexes". J. Biol. Chem. 278 (25): 23101–6. doi:10.1074/jbc.M301021200. PMID12672800.
↑Na SY, Kim HJ, Lee SK, Choi HS, Na DS, Lee MO, Chung M, Moore DD, Lee JW (February 1998). "IkappaBbeta interacts with the retinoid X receptor and inhibits retinoid-dependent transactivation in lipopolysaccharide-treated cells". J. Biol. Chem. 273 (6): 3212–5. doi:10.1074/jbc.273.6.3212. PMID9452433.
Further reading
Lee JW, Choi HS, Gyuris J, Brent R, Moore DD (1995). "Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor". Mol. Endocrinol. 9 (2): 243–54. doi:10.1210/me.9.2.243. PMID7776974.
Harhaj E, Blaney J, Millhouse S, Sun SC (1996). "Differential effects of I kappa B molecules on Tat-mediated transactivation of HIV-1 LTR". Virology. 216 (1): 284–7. doi:10.1006/viro.1996.0062. PMID8615004.
DiDonato JA, Hayakawa M, Rothwarf DM, Zandi E, Karin M (1997). "A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB". Nature. 388 (6642): 548–54. doi:10.1038/41493. PMID9252186.
McKinsey TA, Chu ZL, Ballard DW (1997). "Phosphorylation of the PEST domain of IkappaBbeta regulates the function of NF-kappaB/IkappaBbeta complexes". J. Biol. Chem. 272 (36): 22377–80. doi:10.1074/jbc.272.36.22377. PMID9278383.
Woronicz JD, Gao X, Cao Z, Rothe M, Goeddel DV (1997). "IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK". Science. 278 (5339): 866–9. doi:10.1126/science.278.5339.866. PMID9346485.
Na SY, Kim HJ, Lee SK, Choi HS, Na DS, Lee MO, Chung M, Moore DD, Lee JW (1998). "IkappaBbeta interacts with the retinoid X receptor and inhibits retinoid-dependent transactivation in lipopolysaccharide-treated cells". J. Biol. Chem. 273 (6): 3212–5. doi:10.1074/jbc.273.6.3212. PMID9452433.
Zandi E, Chen Y, Karin M (1998). "Direct phosphorylation of IkappaB by IKKalpha and IKKbeta: discrimination between free and NF-kappaB-bound substrate". Science. 281 (5381): 1360–3. doi:10.1126/science.281.5381.1360. PMID9721103.
Blázquez MV, Macho A, Ortiz C, Lucena C, López-Cabrera M, Sánchez-Madrid F, Muñoz E (1999). "Extracellular HIV type 1 Tat protein induces CD69 expression through NF-kappaB activation: possible correlation with cell surface Tat-binding proteins". AIDS Res. Hum. Retroviruses. 15 (13): 1209–18. doi:10.1089/088922299310304. PMID10480634.
Wu C, Ghosh S (1999). "beta-TrCP mediates the signal-induced ubiquitination of IkappaBbeta". J. Biol. Chem. 274 (42): 29591–4. doi:10.1074/jbc.274.42.29591. PMID10514424.
Kumar A, Dhawan S, Mukhopadhyay A, Aggarwal BB (2000). "Human immunodeficiency virus-1-tat induces matrix metalloproteinase-9 in monocytes through protein tyrosine phosphatase-mediated activation of nuclear transcription factor NF-kappaB". FEBS Lett. 462 (1–2): 140–4. doi:10.1016/S0014-5793(99)01487-8. PMID10580107.
Fenwick C, Na SY, Voll RE, Zhong H, Im SY, Lee JW, Ghosh S (2000). "A subclass of Ras proteins that regulate the degradation of IkappaB". Science. 287 (5454): 869–73. doi:10.1126/science.287.5454.869. PMID10657303.
Manna SK, Aggarwal BB (2000). "Differential requirement for p56lck in HIV-tat versus TNF-induced cellular responses: effects on NF-kappa B, activator protein-1, c-Jun N-terminal kinase, and apoptosis". J. Immunol. 164 (10): 5156–66. doi:10.4049/jimmunol.164.10.5156. PMID10799874.
Li X, Josef J, Marasco WA (2001). "Hiv-1 Tat can substantially enhance the capacity of NIK to induce IkappaB degradation". Biochem. Biophys. Res. Commun. 286 (3): 587–94. doi:10.1006/bbrc.2001.5442. PMID11511100.
Page M, Tuckerman EM, Li TC, Laird SM (2002). "Expression of nuclear factor kappa B components in human endometrium". J. Reprod. Immunol. 54 (1–2): 1–13. doi:10.1016/S0165-0378(01)00122-X. PMID11839392.