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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 .[ 5] [ 6]
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.[ 6]
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 ).[ 5]
Interactions
NFKBIE has been shown to interact with NFKB2 ,[ 7] RELA ,[ 7] NFKB1 [ 7] REL .[ 7] [ 8] [ 9]
References
^ a b c GRCh38: Ensembl release 89: ENSG00000146232 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000023947 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ a b "Entrez Gene: NFKBIE nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon" .^ a b Whiteside ST, Epinat JC, Rice NR, Israël A (March 1997). "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. doi :10.1093/emboj/16.6.1413 . PMC 1169738 PMID 9135156 . ^ a b c d 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). United States: 6184–90. doi :10.1128/mcb.17.10.6184 . ISSN 0270-7306 . PMC 232469 PMID 9315679 . ^ 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" . Proc. Natl. Acad. Sci. U.S.A. 90 (19). United States: 8962–6. Bibcode :1993PNAS...90.8962K . doi :10.1073/pnas.90.19.8962 . ISSN 0027-8424 . PMC 47481 PMID 8415639 . ^ 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). United States: 3316–22. doi :10.4049/jimmunol.164.6.3316 ISSN 0022-1767 . PMID 10706725 .
Further reading
Hansen SK, Baeuerle PA, Blasi F (1994). "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. doi :10.1128/mcb.14.4.2593 . PMC 358627 PMID 8139561 . Kumar S, Gélinas C (1993). "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. Bibcode :1993PNAS...90.8962K . doi :10.1073/pnas.90.19.8962 . PMC 47481 PMID 8415639 . Whiteside ST, Epinat JC, Rice NR, Israël A (1997). "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. doi :10.1093/emboj/16.6.1413 . PMC 1169738 PMID 9135156 . Curristin SM, Bird KJ, Tubbs RJ, Ruddell A (1997). "VBP and RelA regulate avian leukosis virus long terminal repeat-enhanced transcription in B cells" . J. Virol . 71 (8): 5972–81. doi :10.1128/JVI.71.8.5972-5981.1997 . PMC 191853 PMID 9223487 . Li Z, Nabel GJ (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. doi :10.1128/mcb.17.10.6184 . PMC 232469 PMID 9315679 . Spiecker M, Darius H, Liao JK (2000). "A functional role of I kappa B-epsilon in endothelial cell activation" . J. Immunol . 164 (6): 3316–22. doi :10.4049/jimmunol.164.6.3316 PMID 10706725 . Bourke E, Kennedy EJ, Moynagh PN (2001). "Loss of Ikappa B-beta is associated with prolonged NF-kappa B activity in human glial cells" (PDF) . J. Biol. Chem . 275 (51): 39996–40002. doi :10.1074/jbc.M007693200 . PMID 10998424 . S2CID 56360025 . {{cite journal }}: CS1 maint: unflagged free DOI (link )Lee SH, Hannink M (2002). "Characterization of the nuclear import and export functions of Ikappa B(epsilon)" . J. Biol. Chem . 277 (26): 23358–66. doi :10.1074/jbc.M111559200 PMID 11970947 . Bruno ME, Borchers CH, Dial JM, et al. (2002). "Effects of TCDD upon IkappaB and IKK subunits localized in microsomes by proteomics" . Arch. Biochem. Biophys . 406 (2): 153–64. doi :10.1016/S0003-9861(02)00452-6 . PMID 12361703 . Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. Bibcode :2002PNAS...9916899M . doi :10.1073/pnas.242603899 . PMC 139241 PMID 12477932 . Emmerich F, Theurich S, Hummel M, et al. (2004). "Inactivating I kappa B epsilon mutations in Hodgkin/Reed-Sternberg cells". J. Pathol . 201 (3): 413–20. doi :10.1002/path.1454 . PMID 14595753 . S2CID 33577004 . Bouwmeester T, Bauch A, Ruffner H, et al. (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol . 6 (2): 97–105. doi :10.1038/ncb1086 . PMID 14743216 . S2CID 11683986 . Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature . 437 (7062): 1173–8. Bibcode :2005Natur.437.1173R . doi :10.1038/nature04209 . PMID 16189514 . S2CID 4427026 . Nasu-Nishimura Y, Hayashi T, Ohishi T, et al. (2006). "Role of the Rho GTPase-activating protein RICS in neurite outgrowth" . Genes Cells . 11 (6): 607–14. doi :10.1111/j.1365-2443.2006.00966.x PMID 16716191 . S2CID 7935936 . Stefansson B, Brautigan DL (2006). "Protein phosphatase 6 subunit with conserved Sit4-associated protein domain targets IkappaBepsilon" . J. Biol. Chem . 281 (32): 22624–34. doi :10.1074/jbc.M601772200 PMID 16769727 . Chapman SJ, Khor CC, Vannberg FO, et al. (2007). "IkappaB genetic polymorphisms and invasive pneumococcal disease". Am. J. Respir. Crit. Care Med . 176 (2): 181–7. doi :10.1164/rccm.200702-169OC . PMID 17463416 .
