NFKBIE
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] and REL.[7][8][9]
References
- 1 2 3 GRCh38: Ensembl release 89: ENSG00000146232 - Ensembl, May 2017
- 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000023947 - Ensembl, May 2017
- ↑ "Human PubMed Reference:".
- ↑ "Mouse PubMed Reference:".
- 1 2 "Entrez Gene: NFKBIE nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon".
- 1 2 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. PMC 1169738
. PMID 9135156. doi:10.1093/emboj/16.6.1413. - 1 2 3 4 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. United States. 17 (10): 6184–90. ISSN 0270-7306. PMC 232469 . PMID 9315679. doi: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". Proc. Natl. Acad. Sci. U.S.A. United States. 90 (19): 8962–6. ISSN 0027-8424. PMC 47481 . PMID 8415639. doi:10.1073/pnas.90.19.8962.
- ↑ Spiecker, M; Darius H; Liao J K (March 2000). "A functional role of I kappa B-epsilon in endothelial cell activation". J. Immunol. United States. 164 (6): 3316–22. 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. PMC 358627 . PMID 8139561. doi:10.1128/mcb.14.4.2593.
- 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. PMC 47481 . PMID 8415639. doi:10.1073/pnas.90.19.8962.
- 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. PMC 1169738 . PMID 9135156. doi:10.1093/emboj/16.6.1413.
- 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. 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. PMC 232469 . PMID 9315679. doi:10.1128/mcb.17.10.6184.
- 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. 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.". J. Biol. Chem. 275 (51): 39996–40002. PMID 10998424. doi:10.1074/jbc.M007693200.
- Lee SH, Hannink M (2002). "Characterization of the nuclear import and export functions of Ikappa B(epsilon).". J. Biol. Chem. 277 (26): 23358–66. PMID 11970947. doi:10.1074/jbc.M111559200.
- 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. PMID 12361703. doi:10.1016/S0003-9861(02)00452-6.
- 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. PMC 139241 . PMID 12477932. doi:10.1073/pnas.242603899.
- 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. PMID 14595753. doi:10.1002/path.1454.
- 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. PMID 14743216. doi:10.1038/ncb1086.
- 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. PMID 16189514. doi:10.1038/nature04209.
- 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. PMID 16716191. doi:10.1111/j.1365-2443.2006.00966.x.
- Stefansson B, Brautigan DL (2006). "Protein phosphatase 6 subunit with conserved Sit4-associated protein domain targets IkappaBepsilon.". J. Biol. Chem. 281 (32): 22624–34. PMID 16769727. doi:10.1074/jbc.M601772200.
- 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. PMID 17463416. doi:10.1164/rccm.200702-169OC.
