Protein-coding gene in the species Homo sapiens
IKBKB Identifiers Aliases IKBKB External IDs OMIM :603258 ;MGI :1338071 ;HomoloGene :7782 ;GeneCards :IKBKB ;OMA :IKBKB - orthologs Wikidata
IKK-β also known asinhibitor of nuclear factor kappa-B kinase subunit beta is aprotein that in humans is encoded by theIKBKB (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta)gene .
IKK-β is anenzyme that serves as aprotein subunit ofIκB kinase , which is a component of thecytokine -activatedintracellular signaling pathway involved in triggeringimmune responses . IKK's activity causes activation of atranscription factor known as Nuclear Transcription factor kappa-B orNF-κB . Activated IKK-βphosphorylates a protein called theinhibitor of NF-κBIκB (IκBα ), which binds NF-κB to inhibit its function. Phosphorylated IκB isdegraded via theubiquitination pathway, freeing NF-κB, and allowing its entry into thenucleus of the cell where it activates various genes involved ininflammation and other immune responses.
Clinical significance [ edit ] IKK-β plays a significant role inbrain cells following astroke .[ 5] NF-κB activation by IKK-β is blocked, damaged cells within the brain stay alive, and according to a study performed by theUniversity of Heidelberg and the University of Ulm, the cells even appear to make some recovery.[ 6]
Inhibition of IKK and IKK-related kinases has been investigated as a therapeutic option for the treatment of inflammatory diseases and cancer.[ 7] [ 8]
IKK-β (IKBKB) has been shown tointeract with
HDAC9 ,[ 9] CDC37 ,[ 10] CHUK [ 10] [ 11] [ 12] [ 13] [ 14] [ 15] [ 16] CTNNB1 ,[ 17] FANCA ,[ 12] IKBKG [ 10] [ 15] [ 18] [ 19] [ 20] IRAK1 ,[ 21] [ 22] NFKBIA ,[ 14] [ 23] [ 24] MAP3K14 ,[ 14] [ 25] NFKB1 ,[ 26] [ 27] NFKBIB ,[ 14] NCOA3 ,[ 19] PPM1B ,[ 28] TNFRSF1A ,[ 29] [ 30] TRAF2 .[ 31] [ 32]
^a b c GRCh38: Ensembl release 89: ENSG00000104365 –Ensembl , May 2017^a b c GRCm38: Ensembl release 89: ENSMUSG00000031537 –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 .^ Herrmann O, Baumann B, de Lorenzi R, Muhammad S, Zhang W, Kleesiek J, et al. (December 2005). "IKK mediates ischemia-induced neuronal death".Nature Medicine .11 (12):1322– 9.doi :10.1038/nm1323 .PMID 16286924 .S2CID 28490303 . ^ "Stroke 'cell-death trigger' found" .BBC News . 14 November 2005. RetrievedJune 28, 2007 .^ Llona-Minguez S, Baiget J, Mackay SP (July 2013). "Small-molecule inhibitors of IκB kinase (IKK) and IKK-related kinases".Pharmaceutical Patent Analyst .2 (4):481– 98.doi :10.4155/ppa.13.31 .PMID 24237125 . ^ "SAR113945 published clinical trials" .^ Asare Y, Campbell-James TA, Bokov Y, Yu LL, Prestel M, El Bounkari O, et al. (August 2020)."Histone Deacetylase 9 Activates IKK to Regulate Atherosclerotic Plaque Vulnerability" .Circulation Research .127 (6):811– 823.doi :10.1161/CIRCRESAHA.120.316743 PMID 32546048 .S2CID 219726725 . ^a b c Chen G, Cao P, Goeddel DV (February 2002)."TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90" .Molecular Cell .9 (2):401– 10.doi :10.1016/S1097-2765(02)00450-1 PMID 11864612 . ^ Zandi E, Rothwarf DM, Delhase M, Hayakawa M, Karin M (October 1997)."The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation" .Cell .91 (2):243– 52.doi :10.1016/S0092-8674(00)80406-7 PMID 9346241 .S2CID 6399108 . ^a b Otsuki T, Young DB, Sasaki DT, Pando MP, Li J, Manning A, et al. (2002)."Fanconi anemia protein complex is a novel target of the IKK signalsome" .Journal of Cellular Biochemistry .86 (4):613– 23.doi :10.1002/jcb.10270 .PMID 12210728 .S2CID 42471384 . ^ May MJ, D'Acquisto F, Madge LA, Glöckner J, Pober JS, Ghosh S (September 2000). "Selective inhibition of NF-kappaB activation by a peptide that blocks the interaction of NEMO with the IkappaB kinase complex".Science .289 (5484):1550– 4.Bibcode :2000Sci...289.1550M .doi :10.1126/science.289.5484.1550 .PMID 10968790 . ^a b c d 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.Bibcode :1997Sci...278..866W .doi :10.1126/science.278.5339.866 .PMID 9346485 . ^a b Deng L, Wang C, Spencer E, Yang L, Braun A, You J, et al. (October 2000)."Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain" .Cell .103 (2):351– 61.doi :10.1016/S0092-8674(00)00126-4 PMID 11057907 .S2CID 18154645 . ^ Yeung KC, Rose DW, Dhillon AS, Yaros D, Gustafsson M, Chatterjee D, et al. (November 2001)."Raf kinase inhibitor protein interacts with NF-kappaB-inducing kinase and TAK1 and inhibits NF-kappaB activation" .Molecular and Cellular Biology .21 (21):7207– 17.doi :10.1128/MCB.21.21.7207-7217.2001 .PMC 99896 PMID 11585904 . ^ Lamberti C, Lin KM, Yamamoto Y, Verma U, Verma IM, Byers S,Gaynor RB (November 2001)."Regulation of beta-catenin function by the IkappaB kinases" .The Journal of Biological Chemistry .276 (45):42276– 86.doi :10.1074/jbc.M104227200 PMID 11527961 . ^ Chariot A, Leonardi A, Muller J, Bonif M, Brown K, Siebenlist U (October 2002)."Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases" .The Journal of Biological Chemistry .277 (40):37029– 36.doi :10.1074/jbc.M205069200 PMID 12133833 . ^a b Wu RC, Qin J, Hashimoto Y, Wong J, Xu J, Tsai SY, et al. (May 2002)."Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase" .Molecular and Cellular Biology .22 (10):3549– 61.doi :10.1128/MCB.22.10.3549-3561.2002 .PMC 133790 PMID 11971985 . ^ Shifera AS, Horwitz MS (March 2008). "Mutations in the zinc finger domain of IKK gamma block the activation of NF-kappa B and the induction of IL-2 in stimulated T lymphocytes".Molecular Immunology .45 (6):1633– 45.doi :10.1016/j.molimm.2007.09.036 .PMID 18207244 . ^ Vig E, Green M, Liu Y, Yu KY, Kwon HJ, Tian J, et al. (March 2001)."SIMPL is a tumor necrosis factor-specific regulator of nuclear factor-kappaB activity" .The Journal of Biological Chemistry .276 (11):7859– 66.doi :10.1074/jbc.M010399200 PMID 11096118 . ^ Windheim M, Stafford M, Peggie M, Cohen P (March 2008)."Interleukin-1 (IL-1) induces the Lys63-linked polyubiquitination of IL-1 receptor-associated kinase 1 to facilitate NEMO binding and the activation of IkappaBalpha kinase" .Molecular and Cellular Biology .28 (5):1783– 91.doi :10.1128/MCB.02380-06 .PMC 2258775 PMID 18180283 . ^ Mercurio F, Murray BW, Shevchenko A, Bennett BL, Young DB, Li JW, et al. (February 1999)."IkappaB kinase (IKK)-associated protein 1, a common component of the heterogeneous IKK complex" .Molecular and Cellular Biology .19 (2):1526– 38.doi :10.1128/mcb.19.2.1526 .PMC 116081 PMID 9891086 . ^ Cohen L, Henzel WJ, Baeuerle PA (September 1998). "IKAP is a scaffold protein of the IkappaB kinase complex".Nature .395 (6699):292– 6.Bibcode :1998Natur.395..292C .doi :10.1038/26254 .PMID 9751059 .S2CID 4327300 . ^ Luftig MA, Cahir-McFarland E, Mosialos G, Kieff E (May 2001)."Effects of the NIK aly mutation on NF-kappaB activation by the Epstein-Barr virus latent infection membrane protein, lymphotoxin beta receptor, and CD40" .The Journal of Biological Chemistry .276 (18):14602– 6.doi :10.1074/jbc.C100103200 PMID 11278268 . ^ Heissmeyer V, Krappmann D, Hatada EN, Scheidereit C (February 2001)."Shared pathways of IkappaB kinase-induced SCF(betaTrCP)-mediated ubiquitination and degradation for the NF-kappaB precursor p105 and IkappaBalpha" .Molecular and Cellular Biology .21 (4):1024– 35.doi :10.1128/MCB.21.4.1024-1035.2001 .PMC 99557 PMID 11158290 . ^ Heissmeyer V, Krappmann D, Wulczyn FG, Scheidereit C (September 1999)."NF-kappaB p105 is a target of IkappaB kinases and controls signal induction of Bcl-3-p50 complexes" .The EMBO Journal .18 (17):4766– 78.doi :10.1093/emboj/18.17.4766 .PMC 1171549 PMID 10469655 . ^ Prajapati S, Verma U, Yamamoto Y, Kwak YT, Gaynor RB (January 2004)."Protein phosphatase 2Cbeta association with the IkappaB kinase complex is involved in regulating NF-kappaB activity" .The Journal of Biological Chemistry .279 (3):1739– 46.doi :10.1074/jbc.M306273200 PMID 14585847 . ^ Zhang SQ, Kovalenko A, Cantarella G, Wallach D (March 2000)."Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation" .Immunity .12 (3):301– 11.doi :10.1016/S1074-7613(00)80183-1 PMID 10755617 . ^ Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L (September 2000)."Activation of the NF-kappaB pathway by caspase 8 and its homologs" .Oncogene .19 (39):4451– 60.doi :10.1038/sj.onc.1203812 PMID 11002417 . ^ Devin A, Lin Y, Yamaoka S, Li Z, Karin M (June 2001)."The alpha and beta subunits of IkappaB kinase (IKK) mediate TRAF2-dependent IKK recruitment to tumor necrosis factor (TNF) receptor 1 in response to TNF" .Molecular and Cellular Biology .21 (12):3986– 94.doi :10.1128/MCB.21.12.3986-3994.2001 .PMC 87061 PMID 11359906 . ^ Li S, Wang L, Dorf ME (January 2009)."PKC phosphorylation of TRAF2 mediates IKKalpha/beta recruitment and K63-linked polyubiquitination" .Molecular Cell .33 (1):30– 42.doi :10.1016/j.molcel.2008.11.023 .PMC 2643372 PMID 19150425 .
Activity Regulation Classification Kinetics Types
