NFKBIE explained
Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon, also known as NFKBIE, is a protein which in humans is encoded by the NFKBIE gene.[1] [2]
Function
NFKBIE protein expression is up-regulated following NF-κB activation and during myelopoiesis. NFKBIE is able to inhibit NF-κB-directed transactivation via cytoplasmic retention of REL proteins.[2]
NFKB1 or NFKB2 is bound to REL, RELA, or RELB to form the NF-κB transcription factor complex. The NF-κB complex is inhibited by I-kappa-B proteins (NFKBIA 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, or IKBKB) marks them for destruction via the ubiquitination pathway, thereby allowing activation of the NF-kappa-B complex. Activated NF-κB 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). For some genes, activation requires NF-κB interaction with other transcription factors, such as STAT (see STAT6), AP-1 (JUN), and NFAT (see NFATC1).[1]
Interactions
NFKBIE has been shown to interact with NFKB2,[3] RELA,[3] NFKB1[3] and REL.[3] [4] [5]
Further reading
- Hansen SK, Baeuerle PA, Blasi F . Purification, reconstitution, and I kappa B association of the c-Rel-p65 (RelA) complex, a strong activator of transcription. . Mol. Cell. Biol. . 14 . 4 . 2593–603 . 1994 . 8139561 . 10.1128/mcb.14.4.2593. 358627 .
- Kumar S, Gélinas C . I kappa B alpha-mediated inhibition of v-Rel DNA binding requires direct interaction with the RXXRXRXXC Rel/kappa B DNA-binding motif. . Proc. Natl. Acad. Sci. U.S.A. . 90 . 19 . 8962–6 . 1993 . 8415639 . 10.1073/pnas.90.19.8962 . 47481 . 1993PNAS...90.8962K . free .
- Whiteside ST, Epinat JC, Rice NR, Israël A . I kappa B epsilon, a novel member of the I kappa B family, controls RelA and cRel NF-kappa B activity. . EMBO J. . 16 . 6 . 1413–26 . 1997 . 9135156 . 10.1093/emboj/16.6.1413 . 1169738 .
- Curristin SM, Bird KJ, Tubbs RJ, Ruddell A . VBP and RelA regulate avian leukosis virus long terminal repeat-enhanced transcription in B cells. . J. Virol. . 71 . 8 . 5972–81 . 1997 . 9223487 . 10.1128/JVI.71.8.5972-5981.1997. 191853 .
- Li Z, Nabel GJ . A new member of the I kappaB protein family, I kappaB epsilon, inhibits RelA (p65)-mediated NF-kappaB transcription. . Mol. Cell. Biol. . 17 . 10 . 6184–90 . 1997 . 9315679 . 10.1128/mcb.17.10.6184. 232469 .
- Spiecker M, Darius H, Liao JK . A functional role of I kappa B-epsilon in endothelial cell activation. . J. Immunol. . 164 . 6 . 3316–22 . 2000 . 10706725 . 10.4049/jimmunol.164.6.3316. free .
- Bourke E, Kennedy EJ, Moynagh PN . Loss of Ikappa B-beta is associated with prolonged NF-kappa B activity in human glial cells. . J. Biol. Chem. . 275 . 51 . 39996–40002 . 2001 . 10998424 . 10.1074/jbc.M007693200 . 56360025 . free .
- Lee SH, Hannink M . Characterization of the nuclear import and export functions of Ikappa B(epsilon). . J. Biol. Chem. . 277 . 26 . 23358–66 . 2002 . 11970947 . 10.1074/jbc.M111559200 . free .
- Bruno ME, Borchers CH, Dial JM, etal . Effects of TCDD upon IkappaB and IKK subunits localized in microsomes by proteomics. . Arch. Biochem. Biophys. . 406 . 2 . 153–64 . 2002 . 12361703 . 10.1016/S0003-9861(02)00452-6 .
- Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
- Emmerich F, Theurich S, Hummel M, etal . Inactivating I kappa B epsilon mutations in Hodgkin/Reed-Sternberg cells. . J. Pathol. . 201 . 3 . 413–20 . 2004 . 14595753 . 10.1002/path.1454 . 33577004 .
- Bouwmeester T, Bauch A, Ruffner H, etal . A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. . Nat. Cell Biol. . 6 . 2 . 97–105 . 2004 . 14743216 . 10.1038/ncb1086 . 11683986 .
- Rual JF, Venkatesan K, Hao T, etal . Towards a proteome-scale map of the human protein-protein interaction network. . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
- Nasu-Nishimura Y, Hayashi T, Ohishi T, etal . Role of the Rho GTPase-activating protein RICS in neurite outgrowth. . Genes Cells . 11 . 6 . 607–14 . 2006 . 16716191 . 10.1111/j.1365-2443.2006.00966.x . 7935936 . free .
- Stefansson B, Brautigan DL . Protein phosphatase 6 subunit with conserved Sit4-associated protein domain targets IkappaBepsilon. . J. Biol. Chem. . 281 . 32 . 22624–34 . 2006 . 16769727 . 10.1074/jbc.M601772200 . free .
- Chapman SJ, Khor CC, Vannberg FO, etal . IkappaB genetic polymorphisms and invasive pneumococcal disease. . Am. J. Respir. Crit. Care Med. . 176 . 2 . 181–7 . 2007 . 17463416 . 10.1164/rccm.200702-169OC .
Notes and References
- Web site: Entrez Gene: NFKBIE nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon.
- Whiteside ST, Epinat JC, Rice NR, Israël A . I kappa B epsilon, a novel member of the I kappa B family, controls RelA and cRel NF-kappa B activity . EMBO J. . 16 . 6 . 1413–26 . March 1997 . 9135156 . 1169738 . 10.1093/emboj/16.6.1413 .
- Li . Z . Nabel G J . October 1997 . A new member of the I kappaB protein family, I kappaB epsilon, inhibits RelA (p65)-mediated NF-kappaB transcription . Mol. Cell. Biol. . 17 . 10 . 6184–90 . United States. 0270-7306. 9315679 . 232469 . 10.1128/mcb.17.10.6184.
- Kumar . S . Gélinas C . October 1993 . I kappa B alpha-mediated inhibition of v-Rel DNA binding requires direct interaction with the RXXRXRXXC Rel/kappa B DNA-binding motif . . 90 . 19 . 8962–6 . United States. 0027-8424. 8415639 . 1993PNAS...90.8962K . 10.1073/pnas.90.19.8962 . 47481 . free .
- Spiecker . M . Darius H . Liao J K . March 2000 . A functional role of I kappa B-epsilon in endothelial cell activation . J. Immunol. . 164 . 6 . 3316–22 . United States. 10.4049/jimmunol.164.6.3316 . 0022-1767. 10706725 . free .
