TANK-binding kinase 1: Difference between revisions

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{{Infobox_gene}}
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'''Serine/threonine-protein kinase TBK1''' is an [[enzyme]] that in humans is encoded by the ''TBK1'' [[gene]].<ref name="pmid10581243">{{cite journal |vauthors=Pomerantz JL, Baltimore D | title = NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase | journal = EMBO J | volume = 18 | issue = 23 | pages = 6694–704 |date=January 2000 | pmid = 10581243 | pmc = 1171732 | doi = 10.1093/emboj/18.23.6694 }}</ref><ref name="pmid10783893">{{cite journal |vauthors=Tojima Y, Fujimoto A, Delhase M, Chen Y, Hatakeyama S, Nakayama K, Kaneko Y, Nimura Y, Motoyama N, Ikeda K, Karin M, Nakanishi M | title = NAK is an IkappaB kinase-activating kinase | journal = Nature | volume = 404 | issue = 6779 | pages = 778–82 |date=May 2000 | pmid = 10783893 | pmc =  | doi = 10.1038/35008109 }}</ref><ref name="entrez">{{Cite web| title = Entrez Gene: TBK1 TANK-binding kinase 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=29110| accessdate = }}</ref>
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{{GNF_Protein_box
| image =
| image_source = 
| PDB =
| Name = TANK-binding kinase 1
| HGNCid = 11584
| Symbol = TBK1
| AltSymbols =; FLJ11330; NAK; T2K
| OMIM = 604834
| ECnumber =
| Homologene = 22742
| MGIid = 1929658
| GeneAtlas_image1 = PBB_GE_TBK1_218520_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0004674 |text = protein serine/threonine kinase activity}} {{GNF_GO|id=GO:0004871 |text = signal transducer activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0016740 |text = transferase activity}}
| Component =
| Process = {{GNF_GO|id=GO:0006468 |text = protein amino acid phosphorylation}} {{GNF_GO|id=GO:0007249 |text = I-kappaB kinase/NF-kappaB cascade}} {{GNF_GO|id=GO:0009615 |text = response to virus}} {{GNF_GO|id=GO:0043123 |text = positive regulation of I-kappaB kinase/NF-kappaB cascade}} {{GNF_GO|id=GO:0045087 |text = innate immune response}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 29110
    | Hs_Ensembl = ENSG00000183735
    | Hs_RefseqProtein = NP_037386
    | Hs_RefseqmRNA = NM_013254
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 12
    | Hs_GenLoc_start = 63132167
    | Hs_GenLoc_end = 63182153
    | Hs_Uniprot = Q9UHD2
    | Mm_EntrezGene = 56480
    | Mm_Ensembl = ENSMUSG00000020115
    | Mm_RefseqmRNA = NM_019786
    | Mm_RefseqProtein = NP_062760
    | Mm_GenLoc_db =   
    | Mm_GenLoc_chr = 10
    | Mm_GenLoc_start = 120949520
    | Mm_GenLoc_end = 120989807
    | Mm_Uniprot = Q3THP3
  }}
}}
'''TANK-binding kinase 1''', also known as '''TBK1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: TBK1 TANK-binding kinase 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=29110| accessdate = }}</ref>


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| section_title =  
| section_title =
| summary_text = The NF-kappa-B (NFKB) complex of proteins is inhibited by I-kappa-B (IKB) proteins, which inactivate NFKB by trapping it in the cytoplasm. Phosphorylation of serine residues on the IKB proteins by IKB kinases marks them for destruction via the ubiquitination pathway, thereby allowing activation and nuclear translocation of the NFKB complex. The protein encoded by this gene is similar to IKB kinases and can mediate NFKB activation in response to certain growth factors. For example, the protein can form a complex with the IKB protein TANK and TRAF2 and release the NFKB inhibition caused by TANK.<ref name="entrez">{{cite web | title = Entrez Gene: TBK1 TANK-binding kinase 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=29110| accessdate = }}</ref>
| summary_text = The NF-kappa-B (NFKB) complex of proteins is inhibited by I-kappa-B (IKB) proteins, which inactivate NFKB by trapping it in the cytoplasm. Phosphorylation of serine residues on the IKB proteins by IKB kinases marks them for destruction via the ubiquitination pathway, thereby allowing activation and nuclear translocation of the NFKB complex. The protein encoded by this gene is similar to IKB kinases and can mediate NFKB activation in response to certain growth factors. For example, the protein can form a complex with the IKB protein TANK and TRAF2 and release the NFKB inhibition caused by TANK.<ref name="entrez"/>
}}
}}
==Interactions==
TANK-binding kinase 1 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[NCK1]],<ref name = pmid7706279>{{cite journal | date = March 1995 |vauthors=Chou MM, Hanafusa H | title = A novel ligand for SH3 domains. The Nck adaptor protein binds to a serine/threonine kinase via an SH3 domain | journal = J. Biol. Chem. | volume = 270 | issue = 13 | pages = 7359–64 | pmid = 7706279 | doi = 10.1074/jbc.270.13.7359}}</ref>
* [[TANK (gene)|TANK]],<ref name = pmid10581243 /><ref name = pmid14743216/> and
* [[TRAF2]].<ref name = pmid14743216>{{cite journal | date = February 2004 |vauthors=Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G | title = A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway | journal = Nat. Cell Biol. | volume = 6 | issue = 2 | pages = 97–105 | pmid = 14743216 | doi = 10.1038/ncb1086}}</ref><ref name = pmid10990461>{{cite journal | date = September 2000 |vauthors=Bonnard M, Mirtsos C, Suzuki S, Graham K, Huang J, Ng M, Itié A, Wakeham A, Shahinian A, Henzel WJ, Elia AJ, Shillinglaw W, Mak TW, Cao Z, Yeh WC | title = Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription | journal = EMBO J. | volume = 19 | issue = 18 | pages = 4976–85 | pmid = 10990461 | pmc = 314216 | doi = 10.1093/emboj/19.18.4976}}</ref>
{{Div col end}}
Transcriptional factors activated upon TBK1 activation include IRF3, IRF7 <ref name="pmid = 17599067">{{cite journal|date=Jun 2007|title=Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes.|journal=EMBO J.|volume=26|issue=14|pages=|doi=10.1038/sj.emboj.7601773|pmc=1933404|pmid=17599067|author=Ikeda F}}</ref> and ZEB1.
<ref name=" pmid = 24468793">{{cite journal | author = Liu W | title = Inhibition of TBK1 attenuates radiation-induced epithelial-mesenchymal transition of A549 human lung cancer cells via activation of GSK-3β and repression of ZEB1. | journal = Lab Invest. | volume = 94 | issue = 4 |date=Apr 2014 | pmid = 24468793 | url = http://www.nature.com/labinvest/journal/v94/n4/full/labinvest2013153a.html | pages = 362–370 | doi=10.1038/labinvest.2013.153}}</ref>
== Clinical significance ==
Inhibition of [[IκB kinase]] (IKK) and  IKK-related kinases, [[IKBKE]] (IKKε) and TANK-binding kinase 1 (TBK1), has been investigated as a therapeutic option for the treatment of inflammatory diseases and cancer.<ref name="pmid24237125">{{cite journal |vauthors=Llona-Minguez S, Baiget J, Mackay SP | title = Small-molecule inhibitors of IκB kinase (IKK) and IKK-related kinases | journal = Pharm Pat Anal | volume = 2 | issue = 4 | pages = 481–98 | year = 2013 | pmid = 24237125 | doi = 10.4155/ppa.13.31 }}</ref>


==References==
==References==
{{reflist|2}}
{{Reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{Refbegin| 2}}
{{PBB_Further_reading  
{{PBB_Further_reading
| citations =  
| citations =
*{{cite journal  | author=Chou MM, Hanafusa H |title=A novel ligand for SH3 domains. The Nck adaptor protein binds to a serine/threonine kinase via an SH3 domain. |journal=J. Biol. Chem. |volume=270 |issue= 13 |pages= 7359-64 |year= 1995 |pmid= 7706279 |doi=  }}
*{{Cite journal  |vauthors=Chou MM, Hanafusa H |title=A novel ligand for SH3 domains. The Nck adaptor protein binds to a serine/threonine kinase via an SH3 domain. |journal=J. Biol. Chem. |volume=270 |issue= 13 |pages= 7359–64 |year= 1995 |pmid= 7706279 |doi=  10.1074/jbc.270.13.7359}}
*{{cite journal  | author=Chen ZJ, Parent L, Maniatis T |title=Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity. |journal=Cell |volume=84 |issue= 6 |pages= 853-62 |year= 1996 |pmid= 8601309 |doi=  }}
*{{Cite journal  |vauthors=Chen ZJ, Parent L, Maniatis T |title=Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity. |journal=Cell |volume=84 |issue= 6 |pages= 853–62 |year= 1996 |pmid= 8601309 |doi=10.1016/S0092-8674(00)81064-8 }}
*{{cite journal  | author=Zandi E, Chen Y, Karin M |title=Direct phosphorylation of IkappaB by IKKalpha and IKKbeta: discrimination between free and NF-kappaB-bound substrate. |journal=Science |volume=281 |issue= 5381 |pages= 1360-3 |year= 1998 |pmid= 9721103 |doi= }}
*{{Cite journal  |vauthors=Zandi E, Chen Y, Karin M |title=Direct phosphorylation of IkappaB by IKKalpha and IKKbeta: discrimination between free and NF-kappaB-bound substrate. |journal=Science |volume=281 |issue= 5381 |pages= 1360–3 |year= 1998 |pmid= 9721103 |doi=10.1126/science.281.5381.1360  }}
*{{cite journal | author=Pomerantz JL, Baltimore D |title=NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. |journal=EMBO J. |volume=18 |issue= 23 |pages= 6694-704 |year= 2000 |pmid= 10581243 |doi= 10.1093/emboj/18.23.6694 }}
*{{Cite journal   |vauthors=Bonnard M, Mirtsos C, Suzuki S, etal |title=Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription. |journal=EMBO J. |volume=19 |issue= 18 |pages= 4976–85 |year= 2000 |pmid= 10990461 |doi= 10.1093/emboj/19.18.4976  | pmc=314216 }}
*{{cite journal | author=Tojima Y, Fujimoto A, Delhase M, ''et al.'' |title=NAK is an IkappaB kinase-activating kinase. |journal=Nature |volume=404 |issue= 6779 |pages= 778-82 |year= 2000 |pmid= 10783893 |doi= 10.1038/35008109 }}
*{{Cite journal   |vauthors=Kishore N, Huynh QK, Mathialagan S, etal |title=IKK-i and TBK-1 are enzymatically distinct from the homologous enzyme IKK-2: comparative analysis of recombinant human IKK-i, TBK-1, and IKK-2. |journal=J. Biol. Chem. |volume=277 |issue= 16 |pages= 13840–7 |year= 2002 |pmid= 11839743 |doi= 10.1074/jbc.M110474200 }}
*{{cite journal  | author=Bonnard M, Mirtsos C, Suzuki S, ''et al.'' |title=Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription. |journal=EMBO J. |volume=19 |issue= 18 |pages= 4976-85 |year= 2000 |pmid= 10990461 |doi= 10.1093/emboj/19.18.4976 }}
*{{Cite journal   |vauthors=Chariot A, Leonardi A, Muller J, etal |title=Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases. |journal=J. Biol. Chem. |volume=277 |issue= 40 |pages= 37029–36 |year= 2002 |pmid= 12133833 |doi= 10.1074/jbc.M205069200 }}
*{{cite journal | author=Kishore N, Huynh QK, Mathialagan S, ''et al.'' |title=IKK-i and TBK-1 are enzymatically distinct from the homologous enzyme IKK-2: comparative analysis of recombinant human IKK-i, TBK-1, and IKK-2. |journal=J. Biol. Chem. |volume=277 |issue= 16 |pages= 13840-7 |year= 2002 |pmid= 11839743 |doi= 10.1074/jbc.M110474200 }}
*{{Cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 }}
*{{cite journal | author=Chariot A, Leonardi A, Muller J, ''et al.'' |title=Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases. |journal=J. Biol. Chem. |volume=277 |issue= 40 |pages= 37029-36 |year= 2002 |pmid= 12133833 |doi= 10.1074/jbc.M205069200 }}
*{{Cite journal   |vauthors=Li SF, Fujita F, Hirai M, etal |title=Genomic structure and characterization of the promoter region of the human NAK gene. |journal=Gene |volume=304 |issue= |pages= 57–64 |year= 2003 |pmid= 12568715 |doi=10.1016/S0378-1119(02)01179-4  }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{Cite journal   |vauthors=Fitzgerald KA, McWhirter SM, Faia KL, etal |title=IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. |journal=Nat. Immunol. |volume=4 |issue= 5 |pages= 491–6 |year= 2003 |pmid= 12692549 |doi= 10.1038/ni921 }}
*{{cite journal | author=Li SF, Fujita F, Hirai M, ''et al.'' |title=Genomic structure and characterization of the promoter region of the human NAK gene. |journal=Gene |volume=304 |issue= |pages= 57-64 |year= 2003 |pmid= 12568715 |doi= }}
*{{Cite journal   |vauthors=Sharma S, tenOever BR, Grandvaux N, etal |title=Triggering the interferon antiviral response through an IKK-related pathway. |journal=Science |volume=300 |issue= 5622 |pages= 1148–51 |year= 2003 |pmid= 12702806 |doi= 10.1126/science.1081315 }}
*{{cite journal | author=Fitzgerald KA, McWhirter SM, Faia KL, ''et al.'' |title=IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. |journal=Nat. Immunol. |volume=4 |issue= 5 |pages= 491-6 |year= 2003 |pmid= 12692549 |doi= 10.1038/ni921 }}
*{{Cite journal   |vauthors=Matsuda A, Suzuki Y, Honda G, etal |title=Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways. |journal=Oncogene |volume=22 |issue= 21 |pages= 3307–18 |year= 2003 |pmid= 12761501 |doi= 10.1038/sj.onc.1206406 }}
*{{cite journal | author=Sharma S, tenOever BR, Grandvaux N, ''et al.'' |title=Triggering the interferon antiviral response through an IKK-related pathway. |journal=Science |volume=300 |issue= 5622 |pages= 1148-51 |year= 2003 |pmid= 12702806 |doi= 10.1126/science.1081315 }}
*{{Cite journal   |vauthors=Sato S, Sugiyama M, Yamamoto M, etal |title=Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling. |journal=J. Immunol. |volume=171 |issue= 8 |pages= 4304–10 |year= 2004 |pmid= 14530355 |doi= 10.4049/jimmunol.171.8.4304}}
*{{cite journal | author=Matsuda A, Suzuki Y, Honda G, ''et al.'' |title=Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways. |journal=Oncogene |volume=22 |issue= 21 |pages= 3307-18 |year= 2003 |pmid= 12761501 |doi= 10.1038/sj.onc.1206406 }}
*{{Cite journal   |vauthors=Fujita F, Taniguchi Y, Kato T, etal |title=Identification of NAP1, a regulatory subunit of IkappaB kinase-related kinases that potentiates NF-kappaB signaling. |journal=Mol. Cell. Biol. |volume=23 |issue= 21 |pages= 7780–93 |year= 2003 |pmid= 14560022 |doi=10.1128/MCB.23.21.7780-7793.2003  | pmc=207563  }}
*{{cite journal | author=Sato S, Sugiyama M, Yamamoto M, ''et al.'' |title=Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling. |journal=J. Immunol. |volume=171 |issue= 8 |pages= 4304-10 |year= 2004 |pmid= 14530355 |doi= }}
*{{Cite journal  |vauthors=Ota T, Suzuki Y, Nishikawa T, etal |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal | author=Fujita F, Taniguchi Y, Kato T, ''et al.'' |title=Identification of NAP1, a regulatory subunit of IkappaB kinase-related kinases that potentiates NF-kappaB signaling. |journal=Mol. Cell. Biol. |volume=23 |issue= 21 |pages= 7780-93 |year= 2003 |pmid= 14560022 |doi= }}
*{{Cite journal   |vauthors=Bouwmeester T, Bauch A, Ruffner H, etal |title=A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. |journal=Nat. Cell Biol. |volume=6 |issue= 2 |pages= 97–105 |year= 2004 |pmid= 14743216 |doi= 10.1038/ncb1086 }}
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{Cite journal   |vauthors=tenOever BR, Sharma S, Zou W, etal |title=Activation of TBK1 and IKKvarepsilon kinases by vesicular stomatitis virus infection and the role of viral ribonucleoprotein in the development of interferon antiviral immunity. |journal=J. Virol. |volume=78 |issue= 19 |pages= 10636–49 |year= 2004 |pmid= 15367631 |doi= 10.1128/JVI.78.19.10636-10649.2004  | pmc=516426 }}
*{{cite journal | author=Bouwmeester T, Bauch A, Ruffner H, ''et al.'' |title=A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. |journal=Nat. Cell Biol. |volume=6 |issue= 2 |pages= 97-105 |year= 2004 |pmid= 14743216 |doi= 10.1038/ncb1086 }}
*{{Cite journal   |vauthors=Kuai J, Wooters J, Hall JP, etal |title=NAK is recruited to the TNFR1 complex in a TNFalpha-dependent manner and mediates the production of RANTES: identification of endogenous TNFR-interacting proteins by a proteomic approach. |journal=J. Biol. Chem. |volume=279 |issue= 51 |pages= 53266–71 |year= 2005 |pmid= 15485837 |doi= 10.1074/jbc.M411037200 }}
*{{cite journal | author=tenOever BR, Sharma S, Zou W, ''et al.'' |title=Activation of TBK1 and IKKvarepsilon kinases by vesicular stomatitis virus infection and the role of viral ribonucleoprotein in the development of interferon antiviral immunity. |journal=J. Virol. |volume=78 |issue= 19 |pages= 10636-49 |year= 2004 |pmid= 15367631 |doi= 10.1128/JVI.78.19.10636-10649.2004 }}
*{{Cite journal   |vauthors=Buss H, Dörrie A, Schmitz ML, etal |title=Constitutive and interleukin-1-inducible phosphorylation of p65 NF-<nowiki/>{kappa}B at serine 536 is mediated by multiple protein kinases including I{kappa}B kinase (IKK)-<nowiki/>{alpha}, IKK{beta}, IKK{epsilon}, TRAF family member-associated (TANK)-binding kinase 1 (TBK1), and an unknown kinase and couples p65 to TATA-binding protein-associated factor II31-mediated interleukin-8 transcription. |journal=J. Biol. Chem. |volume=279 |issue= 53 |pages= 55633–43 |year= 2005 |pmid= 15489227 |doi= 10.1074/jbc.M409825200 }}
*{{cite journal  | author=Kuai J, Wooters J, Hall JP, ''et al.'' |title=NAK is recruited to the TNFR1 complex in a TNFalpha-dependent manner and mediates the production of RANTES: identification of endogenous TNFR-interacting proteins by a proteomic approach. |journal=J. Biol. Chem. |volume=279 |issue= 51 |pages= 53266-71 |year= 2005 |pmid= 15485837 |doi= 10.1074/jbc.M411037200 }}
}}
*{{cite journal  | author=Buss H, Dörrie A, Schmitz ML, ''et al.'' |title=Constitutive and interleukin-1-inducible phosphorylation of p65 NF-{kappa}B at serine 536 is mediated by multiple protein kinases including I{kappa}B kinase (IKK)-{alpha}, IKK{beta}, IKK{epsilon}, TRAF family member-associated (TANK)-binding kinase 1 (TBK1), and an unknown kinase and couples p65 to TATA-binding protein-associated factor II31-mediated interleukin-8 transcription. |journal=J. Biol. Chem. |volume=279 |issue= 53 |pages= 55633-43 |year= 2005 |pmid= 15489227 |doi= 10.1074/jbc.M409825200 }}
{{Refend}}
 
{{Serine/threonine-specific protein kinases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}
 
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Revision as of 11:33, 15 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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View/Edit Human

Serine/threonine-protein kinase TBK1 is an enzyme that in humans is encoded by the TBK1 gene.[1][2][3]

The NF-kappa-B (NFKB) complex of proteins is inhibited by I-kappa-B (IKB) proteins, which inactivate NFKB by trapping it in the cytoplasm. Phosphorylation of serine residues on the IKB proteins by IKB kinases marks them for destruction via the ubiquitination pathway, thereby allowing activation and nuclear translocation of the NFKB complex. The protein encoded by this gene is similar to IKB kinases and can mediate NFKB activation in response to certain growth factors. For example, the protein can form a complex with the IKB protein TANK and TRAF2 and release the NFKB inhibition caused by TANK.[3]

Interactions

TANK-binding kinase 1 has been shown to interact with:

Transcriptional factors activated upon TBK1 activation include IRF3, IRF7 [7] and ZEB1. [8]

Clinical significance

Inhibition of IκB kinase (IKK) and IKK-related kinases, IKBKE (IKKε) and TANK-binding kinase 1 (TBK1), has been investigated as a therapeutic option for the treatment of inflammatory diseases and cancer.[9]

References

  1. ↑ 1.0 1.1 Pomerantz JL, Baltimore D (January 2000). "NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase". EMBO J. 18 (23): 6694–704. doi:10.1093/emboj/18.23.6694. PMC 1171732. PMID 10581243.
  2. ↑ Tojima Y, Fujimoto A, Delhase M, Chen Y, Hatakeyama S, Nakayama K, Kaneko Y, Nimura Y, Motoyama N, Ikeda K, Karin M, Nakanishi M (May 2000). "NAK is an IkappaB kinase-activating kinase". Nature. 404 (6779): 778–82. doi:10.1038/35008109. PMID 10783893.
  3. ↑ 3.0 3.1 "Entrez Gene: TBK1 TANK-binding kinase 1".
  4. ↑ Chou MM, Hanafusa H (March 1995). "A novel ligand for SH3 domains. The Nck adaptor protein binds to a serine/threonine kinase via an SH3 domain". J. Biol. Chem. 270 (13): 7359–64. doi:10.1074/jbc.270.13.7359. PMID 7706279.
  5. ↑ 5.0 5.1 Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (February 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.
  6. ↑ Bonnard M, Mirtsos C, Suzuki S, Graham K, Huang J, Ng M, Itié A, Wakeham A, Shahinian A, Henzel WJ, Elia AJ, Shillinglaw W, Mak TW, Cao Z, Yeh WC (September 2000). "Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription". EMBO J. 19 (18): 4976–85. doi:10.1093/emboj/19.18.4976. PMC 314216. PMID 10990461.
  7. ↑ Ikeda F (Jun 2007). "Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes". EMBO J. 26 (14). doi:10.1038/sj.emboj.7601773. PMC 1933404. PMID 17599067.
  8. ↑ Liu W (Apr 2014). "Inhibition of TBK1 attenuates radiation-induced epithelial-mesenchymal transition of A549 human lung cancer cells via activation of GSK-3β and repression of ZEB1". Lab Invest. 94 (4): 362–370. doi:10.1038/labinvest.2013.153. PMID 24468793.
  9. ↑ Llona-Minguez S, Baiget J, Mackay SP (2013). "Small-molecule inhibitors of IκB kinase (IKK) and IKK-related kinases". Pharm Pat Anal. 2 (4): 481–98. doi:10.4155/ppa.13.31. PMID 24237125.

Further reading

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