Affinage

TANK

TRAF family member-associated NF-kappa-B activator · UniProt Q92844

Audit flag: ungrounded claim
Length
425 aa
Mass
47.8 kDa
Annotated
2026-06-10
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TANK (I-TRAF) is an intracellular scaffold/adaptor protein that integrates TRAF-family signaling to both activate and restrain NF-κB and type I interferon induction (PMID:8710854, PMID:8608943, PMID:10581243). It engages the conserved TRAF-C domains of TRAF1, TRAF2, and TRAF3 through a boomerang-shaped PxQxT-like recognition motif that occupies the same TRAF crevice used by receptor tails such as CD40, allowing TANK to compete for TRAF binding (PMID:8710854, PMID:8608943, PMID:12005438, PMID:28155233). Through an N-terminal region TANK nucleates a ternary complex with the IKK-related kinase TBK1 and TRAF2 that is required for TBK1 kinase activity, and a shared TBK1/IKKε-binding domain places TANK among a set of adaptors (with SINTBAD and NAP1) that couple these kinases to virus-activated, IRF-dependent transcription (PMID:10581243, PMID:17568778). As part of a TRAF3-containing complex it assembles TBK1/IKKε to drive IRF3/7 phosphorylation in selected TLR pathways (PMID:17823124); genetic studies refine this role, showing TANK is essential for IKKε activation and for cross-talk between IKK-related and canonical IKKs while being dispensable for IRF3 phosphorylation and IFNβ production in macrophages (PMID:21949249). TANK also functions as a brake on NF-κB: it recruits PLK1 to a TANK·NEMO complex to suppress NEMO ubiquitination and TNF-induced IKK activation (PMID:20484576), assembles a TANK·MCPIP1·USP10 complex that deubiquitinates TRAF6 to resolve genotoxic, IL-1β, and LPS-driven NF-κB signaling (PMID:25861989), and limits non-canonical NF-κB downstream of TACI (PMID:20394400). Its activity is dynamically tuned by post-translational modification—IKKβ, IKKε, and TBK1 phosphorylation, K63-linked and mono-ubiquitination, and SUMOylation at the conserved Lys282, the last weakening the TANK–IKKε interaction to relieve TANK's inhibitory function during TLR7 signaling (PMID:10759890, PMID:16336209, PMID:17823124, PMID:21212807, PMID:22330071). Knockout mice reveal physiological roles as a negative regulator of RANKL-induced osteoclastogenesis, where TANK loss elevates TRAF6 ubiquitination and causes trabecular bone loss (PMID:22773835). TANK is also a target of viral immune evasion: SARS coronavirus M protein blocks TRAF3·TANK·TBK1/IKKε complex assembly, and multiple picornavirus 3C proteases cleave TANK to relieve its restraint on TRAF6-mediated NF-κB signaling (PMID:19380580, PMID:26363073, PMID:28566380).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1996 High

    Established that TANK physically links to the TRAF machinery and can negatively regulate TRAF-driven NF-κB, defining it as an intrinsic modulator of TRAF function.

    Evidence Yeast two-hybrid, Co-IP, and NF-κB reporter assays identifying binding to TRAF-C domains of TRAF1/2/3 and inhibition of TRAF2-mediated NF-κB

    PMID:8608943 PMID:8710854

    Open questions at the time
    • Whether TANK is activating or inhibitory in physiological context not resolved by overexpression
    • Endogenous stoichiometry with TRAFs unknown
  2. 1996 High

    Resolved the dual activating/inhibitory behavior by mapping it to TANK domains, showing an autoinhibitory C-terminus relieved by TRAF2 binding.

    Evidence Cotransfection NF-κB reporter assays with deletion mutants

    PMID:8608943

    Open questions at the time
    • Molecular basis of the C-terminal autoinhibition not structurally defined
    • Native trigger for switching states unknown
  3. 1999 High

    Identified the TBK1 kinase as a TANK partner and showed a TBK1-TANK-TRAF2 ternary complex is required for kinase activity, placing TANK upstream of the IKK complex.

    Evidence Reciprocal Co-IP, kinase-dead dominant-negative constructs, NF-κB reporter epistasis

    PMID:10581243

    Open questions at the time
    • How complex assembly activates TBK1 catalytically not defined
    • Receptor inputs that nucleate the complex not mapped
  4. 2000 Medium

    Demonstrated kinase-driven regulation of TANK assembly: IKKε phosphorylates TANK to release TRAF2, providing a feedback mechanism.

    Evidence Yeast two-hybrid, in vitro kinase assay, Co-IP, dominant-negative overexpression

    PMID:10759890

    Open questions at the time
    • Phosphosite residues not precisely mapped
    • Single-lab in vitro phosphorylation, not validated in cells under physiological stimulation
  5. 2002 High

    Provided atomic-level basis for TANK-TRAF recognition, showing TANK uses a boomerang-shaped PxQxT motif competing with receptor tails for the TRAF crevice.

    Evidence X-ray crystallography of TANK peptide bound to TRAF3, mutagenesis, ITC, competition assays

    PMID:12005438

    Open questions at the time
    • Structure limited to a peptide, not full-length TANK
    • Conformational dynamics of the intact complex unaddressed
  6. 2006 Medium

    Defined a C-terminal zinc finger mediating TNF-induced recruitment to the IKK complex and IKKβ phosphorylation that regulates NEMO binding, linking TANK to canonical TNF signaling.

    Evidence Co-IP, RNAi knockdown, NF-κB reporter assays, domain mapping

    PMID:16336209

    Open questions at the time
    • IKKβ phosphosite not mapped
    • Single-lab RNAi, mechanism of p65 transactivation modulation unclear
  7. 2006 Low

    Identified TFG as a TANK interactor enhancing NF-κB activation, expanding the TANK interactome.

    Evidence Yeast two-hybrid, Co-IP, NF-κB reporter assay

    PMID:16547966

    Open questions at the time
    • Single Co-IP/Y2H in one lab with limited TANK-specific follow-up
    • Physiological relevance of TFG-TANK axis untested
  8. 2007 High

    Established TANK as a scaffold assembling TBK1/IKKε within a TRAF3 complex for IRF3/7 phosphorylation, and characterized LPS-induced phosphorylation and K63-ubiquitination.

    Evidence Co-IP, in vitro kinase assay, RNAi, ubiquitin linkage analysis

    PMID:17823124

    Open questions at the time
    • Ubiquitin ligase responsible for K63 chains not identified
    • Pathway selectivity (some but not all TLRs) not fully explained
  9. 2007 High

    Showed TANK is one of several redundant adaptors (with SINTBAD, NAP1) sharing a conserved TBK1/IKKi-binding domain, contextualizing its role in virus-activated signaling.

    Evidence Co-IP, TBD competition assays, siRNA, IRF-dependent reporter assays

    PMID:17568778

    Open questions at the time
    • Functional non-redundancy among the three adaptors not resolved
    • Determinants of adaptor selection in vivo unknown
  10. 2009 Medium

    Revealed TANK as a target of viral immune evasion, with SARS-CoV M protein blocking TRAF3·TANK·TBK1/IKKε complex assembly to suppress interferon.

    Evidence Co-IP, IRF-dependent reporter assays, overexpression

    PMID:19380580

    Open questions at the time
    • Direct binding partner of M protein within the complex not pinpointed
    • Overexpression-based, single lab
  11. 2010 Medium

    Defined a negative-regulatory mechanism whereby TANK scaffolds PLK1 into a complex with NEMO to suppress NEMO ubiquitination and TNF-induced IKK activation.

    Evidence Reciprocal Co-IP, ubiquitination assays, NF-κB reporter and DNA-binding assays

    PMID:20484576

    Open questions at the time
    • Whether PLK1 modifies NEMO directly or via recruited factors unclear
    • Single lab
  12. 2010 Medium

    Extended TANK's inhibitory role to non-canonical NF-κB, showing it restrains NIK by promoting cIAP1-mediated NIK ubiquitination downstream of TACI.

    Evidence siRNA knockdown, Co-IP, ubiquitination assays, NF-κB reporter assays

    PMID:20394400

    Open questions at the time
    • Mechanism by which TANK inhibits TRAF2-mediated cIAP1 inactivation not detailed
    • Single lab, siRNA-based
  13. 2011 High

    Genetic knockout dissected TANK's roles, showing it is essential for IKKε activation and IKK-related/canonical IKK cross-talk but dispensable for IRF3 phosphorylation and IFNβ production in macrophages.

    Evidence TANK knockout macrophages, kinase activity assays, Co-IP, IRF3 phosphorylation, IFNβ ELISA

    PMID:21949249

    Open questions at the time
    • Redundancy with SINTBAD/NAP1 in IFN production not directly tested here
    • Cell-type specificity of the dispensability for IFN unclear
  14. 2011 High

    Identified SUMOylation at conserved Lys282, induced by IKKε/TBK1, as a switch that weakens TANK-IKKε binding to relieve TANK's negative function during TLR7 signaling.

    Evidence SUMOylation assays, K282 mutagenesis, Co-IP, reconstitution in TANK-deficient cells, reporter assays

    PMID:21212807 PMID:23201825

    Open questions at the time
    • SUMO ligase responsible not identified
    • Interplay between SUMOylation and phosphorylation/ubiquitination not integrated
  15. 2012 High

    Knockout mice revealed TANK as a physiological negative regulator of osteoclastogenesis, restraining TRAF6 ubiquitination and protecting against bone loss.

    Evidence TANK knockout mice, osteoclast differentiation, ubiquitination and NF-κB assays, bone histomorphometry

    PMID:22773835

    Open questions at the time
    • Molecular mechanism limiting TRAF6 ubiquitination not fully defined here
    • Relationship to the later USP10 deubiquitination mechanism not linked
  16. 2012 Medium

    Showed mono-ubiquitination of TANK (by Pellino3 downstream of oxLDL/SR-A1) blocks TBK1 recruitment to TRAF3, defining an ubiquitin-based control of TANK scaffold function.

    Evidence Co-IP, ubiquitination assays, RNAi, IRF3 activation assays

    PMID:22330071

    Open questions at the time
    • Mono-ubiquitination acceptor site on TANK not mapped
    • Single lab
  17. 2015 High

    Defined a TANK·MCPIP1·USP10 complex that deubiquitinates TRAF6 to resolve genotoxic, IL-1β, and LPS-driven NF-κB, giving a molecular mechanism for TANK's negative regulation.

    Evidence CRISPR/Cas9 knockout, Co-IP, ubiquitination assays, NF-κB reporter assays

    PMID:25861989

    Open questions at the time
    • How DNA damage signals reach the cytoplasmic complex not detailed
    • Stoichiometry and assembly order of the trimeric complex unknown
  18. 2017 High

    Provided structural and quantitative detail of TANK-TRAF1 binding, confirming the Px(Q/E)xT motif and comparable micromolar affinity for TRAF1 and TRAF2.

    Evidence X-ray crystallography (PDB 5H10), ITC, quantitative binding assays

    PMID:28155233

    Open questions at the time
    • Functional consequence of TANK-TRAF1 binding specifically not addressed
    • Peptide-level structure only
  19. 2017 Medium

    Established TANK as a recurrent picornavirus protease target, with EMCV and Seneca Valley virus 3C proteases cleaving TANK to relieve its restraint on TRAF6-mediated NF-κB and impair IFN regulation.

    Evidence In vitro protease cleavage assays, cleavage-site mutagenesis, NF-κB and IFN reporter assays

    PMID:26363073 PMID:28566380

    Open questions at the time
    • Cleavage demonstrated largely in vitro/overexpression
    • Consequences for viral fitness in vivo not established
  20. 2019 Medium

    Extended TANK's physiological scope to the nervous system, linking it to cortical NF-κB-dependent neuroimmune signaling and alcohol/anxiety behaviors.

    Evidence TANK knockout mice, behavioral assays, NF-κB activation in brain tissue

    PMID:30721969

    Open questions at the time
    • Neuronal cell-type-specific contribution not dissected
    • Causal link between cortical NF-κB and behavior correlative
  21. 2022 Medium

    Defined a PLK1/TANK/NF-κB axis in intestinal epithelium, where TANK opposes PLK1's protective effect against LPS-induced epithelial injury, mitochondrial dysfunction, and apoptosis.

    Evidence Co-IP, siRNA knockdown, NF-κB and mitochondrial/apoptosis assays, in vivo CLP model

    PMID:36581806

    Open questions at the time
    • Mechanistic relationship to the earlier PLK1-NEMO model not integrated
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TANK's opposing activating and inhibitory functions are selected within a given pathway, cell type, and post-translational modification state remains unresolved.
  • No integrated model linking phosphorylation, ubiquitination, and SUMOylation to functional switching
  • Tissue-specific roles (bone, brain, gut) lack a unifying mechanism
  • No full-length TANK structure to explain conformational regulation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 5 GO:0005198 structural molecule activity 3
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4
Partners
IKKΕNEMOPLK1TBK1TRAF1TRAF2TRAF3USP10
Complex memberships
PLK1·TANK·NEMO complexTANK·MCPIP1·USP10 complexTBK1·TANK·TRAF2 complexTRAF3·TANK·TBK1/IKKε complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 TANK (I-TRAF) was identified as a novel intracellular protein that binds to the conserved TRAF-C domain of TRAF1, TRAF2, and TRAF3. Overexpression of I-TRAF inhibits TRAF2-mediated NF-κB activation downstream of CD40 and both TNF receptors, suggesting TANK acts as a natural regulator of TRAF function by maintaining TRAFs in a latent state. Yeast two-hybrid screening, co-immunoprecipitation, cotransfection NF-κB reporter assays Proceedings of the National Academy of Sciences of the United States of America High 8608943 8710854
1996 TANK and TRAF2 synergistically activate NF-κB in cotransfection experiments. This synergistic activation requires both the amino-terminal portion of TANK and the RING finger domain of TRAF2. TANK has an internally inhibitory carboxyl terminus, and TRAF2 binding overcomes this internal inhibition. Cotransfection NF-κB luciferase reporter assays, deletion mutagenesis Genes & development High 8608943
1999 TANK interacts with TBK1 (TANK-binding kinase 1), a novel IKK-related kinase. TBK1, TANK, and TRAF2 form a ternary complex, and complex formation is required for TBK1 kinase activity. Kinase-inactive TBK1 inhibits TANK-mediated NF-κB activation but does not block TNF-α, IL-1, or CD40 signaling, positioning the TBK1-TANK-TRAF2 complex upstream of NIK and the IKK complex. Co-immunoprecipitation, kinase-dead dominant-negative constructs, NF-κB reporter assays, genetic epistasis The EMBO journal High 10581243
2000 IKK-i (IKKε) phosphorylates TANK/I-TRAF in vitro in the middle portion of TANK that associates with TRAF2. Following IKK-i-mediated phosphorylation of TANK, TRAF2 is released from the TANK/TRAF2 complex. The N-terminal domain of TANK mediates its interaction with the C-terminal portion of IKK-i, and NF-κB activation by IKK-i is blocked by co-expression of the N-terminal domain of TANK. Yeast two-hybrid (IKK-i/TANK interaction), in vitro kinase assay, co-immunoprecipitation, dominant-negative overexpression Genes to cells : devoted to molecular & cellular mechanisms Medium 10759890
2002 Crystal structure of a TANK peptide bound to TRAF3 was determined, showing that TANK and CD40 bind to the same crevice on TRAF3. TANK presents a boomerang-like structure at the recognition motif PxQxT that is distinct from the hairpin loop of CD40. Mutagenesis confirmed critical TANK contact residues for binding to TRAF3 and TRAF2; TANK competes with CD40 for the TRAF binding site as demonstrated by isothermal titration calorimetry and competition assays. X-ray crystallography, site-directed mutagenesis, isothermal titration calorimetry, competition binding assays Structure (London, England : 1993) High 12005438
2006 TNF-α stimulation promotes TANK recruitment to the IKK complex via a newly characterized C-terminal zinc finger in TANK. IKKβ phosphorylates TANK upon TNF-α stimulation, and this phosphorylation negatively regulates TANK binding to NEMO. Reduced TANK expression (by RNAi) attenuates TNF-α-mediated induction of a subset of NF-κB target genes through decreased p65 transactivation potential. Co-immunoprecipitation, RNAi knockdown, NF-κB reporter assays, domain mapping The Biochemical journal Medium 16336209
2006 TFG (TRK-fused gene) was identified as a novel TANK-interacting protein through yeast two-hybrid screening and confirmed by in vitro and in vivo co-immunoprecipitation. TFG and NEMO may be part of the same high molecular weight complex. TFG enhances TANK-induced NF-κB activation. Yeast two-hybrid, co-immunoprecipitation, NF-κB reporter assay Journal of cellular physiology Low 16547966
2007 TANK was identified as a scaffold protein that assembles TBK1/IKKε complexes required for IRF3/7 phosphorylation in some (but not all) Toll-like receptor-dependent signaling pathways. TANK is part of a TRAF3-containing complex. Upon LPS stimulation, TANK is heavily phosphorylated by TBK1-IKKε and undergoes Lys63-linked polyubiquitination in a manner that does not require TBK1-IKKε kinase activity. Co-immunoprecipitation, in vitro kinase assay, RNAi knockdown, ubiquitin linkage analysis The Journal of biological chemistry High 17823124
2007 SINTBAD, NAP1, and TANK share a conserved TBK1/IKKi-binding domain (TBD) predicted to form an alpha-helix with residues essential for kinase binding on one face. Isolated TBDs from each adaptor compete with each other for binding to TBK1 and prevent poly(I:C)-induced IRF-dependent transcription, establishing TANK as one of multiple adaptors linking TBK1/IKKi to virus-activated signaling. Co-immunoprecipitation, competition assays, siRNA knockdown, IRF-dependent transcription reporter assay The EMBO journal High 17568778
2009 SARS coronavirus M protein physically associates with TRAF3, TBK1, IKKε, and RIG-I, and prevents formation of the TRAF3·TANK·TBK1/IKKε complex, thereby inhibiting TBK1/IKKε-dependent activation of IRF3/IRF7 and type I interferon production. M protein has no influence when IRF3 or IRF7 are overexpressed directly, indicating the block is upstream at complex assembly. Co-immunoprecipitation, IRF-dependent transcription reporter assay, overexpression studies The Journal of biological chemistry Medium 19380580
2010 TANK directly interacts with PLK1 (polo-like kinase 1). PLK1, TANK, and NEMO (IKKγ) form a ternary complex in vivo. PLK1 negatively regulates TNF-induced IKK activation by inhibiting ubiquitination of NEMO, establishing TANK as a scaffold that recruits PLK1 to suppress NF-κB signaling. Co-immunoprecipitation, ubiquitination assay, NF-κB reporter assays, NF-κB DNA-binding assay Molecular biology of the cell Medium 20484576
2010 TANK participates in limiting non-canonical NF-κB signaling downstream of TACI. TANK deficiency (by siRNA) impairs TACI-dependent inhibition of NF-κB2 p100 processing. TANK inhibits TRAF2-mediated cIAP1 inactivation and thereby facilitates cIAP1-mediated ubiquitination of NIK to suppress non-canonical NF-κB signaling. siRNA knockdown, co-immunoprecipitation, ubiquitination assays, NF-κB reporter assays Journal of receptor and signal transduction research Medium 20394400
2011 TANK is required for the activation of IKKε and for optimal activation of TBK1 in macrophages stimulated through both MyD88- and TRIF-dependent TLR pathways. TANK is required for the interaction between IKK-related kinases and canonical IKKs, enabling IKK-related kinases to negatively regulate canonical IKKs. In TANK−/− macrophages, IKKε activation is abolished, TBK1 activation is reduced, but IRF3 phosphorylation and IFNβ production remain normal. TANK knockout macrophages, kinase activity assays, co-immunoprecipitation, IRF3 phosphorylation assays, IFNβ ELISA Proceedings of the National Academy of Sciences of the United States of America High 21949249
2011 SUMOylation of TANK at the evolutionarily conserved Lys282 is triggered by IKKε and TBK1 kinase activities. Stimulation of TLR7 induces TANK SUMOylation, which weakens the interaction between TANK and IKKε, thereby relieving TANK's negative function on TLR7 signal propagation. Reconstitution experiments show that absence of TANK SUMOylation impairs inducible expression of TLR7-dependent target genes. SUMOylation assays, site-directed mutagenesis (K282), co-immunoprecipitation, reconstitution in TANK-deficient cells, reporter assays EMBO reports High 21212807
2012 TANK is a negative regulator of osteoclast differentiation. TANK expression is upregulated during RANKL-induced osteoclastogenesis. Tank−/− cells show increased osteoclastogenesis with increased TRAF6 ubiquitination and enhanced canonical NF-κB activation in response to RANKL. Tank−/− mice develop severe trabecular bone loss due to enhanced bone erosion. TANK knockout mouse model, osteoclast differentiation assays, ubiquitination assays, NF-κB activation assays, bone histomorphometry The Journal of biological chemistry High 22773835
2012 In the context of virus-triggered signaling, TANK mono-ubiquitination (mediated by Pellino3 downstream of IRAK1/4 via SR-A1) inhibits TBK1 recruitment to TRAF3, thereby blocking TBK1-TRAF3 interaction and subsequent IRF3 activation and IFNβ expression. oxLDL stimulates this TANK mono-ubiquitination pathway. Co-immunoprecipitation, ubiquitination assays, RNAi knockdown, IRF3 activation assays Cellular signalling Medium 22330071
2015 TANK negatively regulates genotoxic NF-κB activation by facilitating USP10-dependent deubiquitination of TRAF6. TANK forms a complex with MCPIP1 (ZC3H12A) and the deubiquitinase USP10, which is essential for TRAF6 deubiquitination and resolution of DNA damage-induced NF-κB activation. CRISPR/Cas9 deletion of TANK in human cells enhances NF-κB activation after genotoxic treatment. The TANK-MCPIP1-USP10 complex also decreases TRAF6 ubiquitination downstream of IL-1β and LPS. CRISPR/Cas9 knockout, co-immunoprecipitation, ubiquitination assays, NF-κB reporter assays The Journal of biological chemistry High 25861989
2015 Encephalomyocarditis virus (EMCV) 3C protease cleaves TANK at Q197 and Q291, dependent on 3C cysteine protease activity. Cleavage of TANK by EMCV 3C impairs TANK's ability to inhibit TRAF6-mediated NF-κB signaling. Several other picornavirus proteases (FMDV, PRRSV, EAV) also cleave TANK. In vitro protease cleavage assays, site-directed mutagenesis, NF-κB reporter assays The Journal of biological chemistry Medium 26363073
2017 Crystal structure of the TRAF1/TANK peptide complex was determined (PDB: 5H10). TANK binds TRAF1 using the minor minimal consensus motif Px(Q/E)xT. Quantitative interaction experiments showed TANK peptide interacts with TRAF1 and TRAF2 with similar micromolar affinity. X-ray crystallography, isothermal titration calorimetry, quantitative binding assays FEBS letters High 28155233
2017 Seneca Valley virus 3C protease mediates cleavage of TANK (along with MAVS and TRIF) at specific sites requiring 3C protease activity. Cleaved TANK loses the ability to regulate PRR-mediated IFN production, and TANK cleavage facilitates TRAF6-induced NF-κB activation. In vitro protease cleavage assays, IFN production assays, NF-κB reporter assays Journal of virology Medium 28566380
2011 In the context of TLR7 signaling, TANK SUMOylation (induced by TBK1/IKKε) weakens the TANK-IKKε interaction, thereby relieving TANK's constitutive negative function on downstream signal propagation. Separately, TANK expression is up-regulated in injured sensory neurons (DRG) and is transcriptionally regulated by the injury-associated transcription factor Sox11 via direct binding to two Sox motifs in the TANK 5'-UTR. Chromatin immunoprecipitation, luciferase reporter with Sox site mutagenesis, Sox11 siRNA knockdown, quantitative PCR Neuroscience Medium 23201825
2019 TANK knockout mice display altered alcohol drinking behavior and enhanced anxiety-related behavior, and show increased NF-κB activation in the insular cortex following alcohol exposure, suggesting TANK regulates cortical NF-κB-dependent neuroimmune signaling in the context of aversive emotional processing. Tank knockout mouse model, behavioral assays, NF-κB activation assays in brain tissue Cerebral cortex (New York, N.Y. : 1991) Medium 30721969
2022 PLK1 co-localizes and physically interacts with TANK in intestinal epithelial (Caco-2) cells. TANK overexpression impairs the protective effect of PLK1 on LPS-induced intestinal epithelial injury and NF-κB activation, and TANK siRNA knockdown suppresses NF-κB signaling and ameliorates mitochondrial dysfunction and apoptosis induced by LPS. This defines a PLK1/TANK/NF-κB axis regulating intestinal barrier function. Co-immunoprecipitation, siRNA knockdown, NF-κB signaling assays, mitochondrial dynamics assays, apoptosis assays, in vivo CLP model Molecular medicine (Cambridge, Mass.) Medium 36581806

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines. Nature 510 18256672
1999 NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. The EMBO journal 504 10581243
1996 TANK, a co-inducer with TRAF2 of TNF- and CD 40L-mediated NF-kappaB activation. Genes & development 253 8608943
2009 Severe acute respiratory syndrome coronavirus M protein inhibits type I interferon production by impeding the formation of TRAF3.TANK.TBK1/IKKepsilon complex. The Journal of biological chemistry 232 19380580
2012 Molecular basis of Tank-binding kinase 1 activation by transautophosphorylation. Proceedings of the National Academy of Sciences of the United States of America 210 22619329
2013 Crystal structure and mechanism of activation of TANK-binding kinase 1. Cell reports 206 23453971
1996 I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated signal transduction. Proceedings of the National Academy of Sciences of the United States of America 189 8710854
2013 Structure and ubiquitination-dependent activation of TANK-binding kinase 1. Cell reports 181 23453972
2011 IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation. Proceedings of the National Academy of Sciences of the United States of America 180 21464307
2007 SINTBAD, a novel component of innate antiviral immunity, shares a TBK1-binding domain with NAP1 and TANK. The EMBO journal 168 17568778
2011 Polyubiquitin binding to optineurin is required for optimal activation of TANK-binding kinase 1 and production of interferon β. The Journal of biological chemistry 151 21862579
2004 Guidelines for monitoring bulk tank milk somatic cell and bacterial counts. Journal of dairy science 149 15377636
2011 The TRAF-associated protein TANK facilitates cross-talk within the IkappaB kinase family during Toll-like receptor signaling. Proceedings of the National Academy of Sciences of the United States of America 115 21949249
2017 Seneca Valley Virus Suppresses Host Type I Interferon Production by Targeting Adaptor Proteins MAVS, TRIF, and TANK for Cleavage. Journal of virology 111 28566380
2018 Lipotoxicity induces hepatic protein inclusions through TANK binding kinase 1-mediated p62/sequestosome 1 phosphorylation. Hepatology (Baltimore, Md.) 97 29251796
2015 TRAF Family Member-associated NF-κB Activator (TANK) Inhibits Genotoxic Nuclear Factor κB Activation by Facilitating Deubiquitinase USP10-dependent Deubiquitination of TRAF6 Ligase. The Journal of biological chemistry 93 25861989
2000 NF-kappaB activation through IKK-i-dependent I-TRAF/TANK phosphorylation. Genes to cells : devoted to molecular & cellular mechanisms 93 10759890
2016 Adaptable stirred-tank culture strategies for large scale production of multicellular spheroid-based tumor cell models. Journal of biotechnology 87 26815388
2015 Tank binding kinase 1 is a centrosome-associated kinase necessary for microtubule dynamics and mitosis. Nature communications 87 26656453
2013 Gene-environment interactions in cancer epidemiology: a National Cancer Institute Think Tank report. Genetic epidemiology 81 24123198
2022 Continuous human iPSC-macrophage mass production by suspension culture in stirred tank bioreactors. Nature protocols 75 35039668
2007 Lipopolysaccharide-mediated interferon regulatory factor activation involves TBK1-IKKepsilon-dependent Lys(63)-linked polyubiquitination and phosphorylation of TANK/I-TRAF. The Journal of biological chemistry 75 17823124
2016 Prevalence of Bovine Mastitis Pathogens in Bulk Tank Milk in China. PloS one 72 27187065
2011 Inhibition of TANK binding kinase 1 by herpes simplex virus 1 facilitates productive infection. Journal of virology 70 22171259
2011 TANK-binding kinase 1 (TBK1) controls cell survival through PAI-2/serpinB2 and transglutaminase 2. Proceedings of the National Academy of Sciences of the United States of America 59 22203995
2018 TANK-Binding Kinase 1-Dependent Responses in Health and Autoimmunity. Frontiers in immunology 57 29559975
2014 Elevated expression of TANK-binding kinase 1 enhances tamoxifen resistance in breast cancer. Proceedings of the National Academy of Sciences of the United States of America 55 24449872
2018 gga-miR-155 Enhances Type I Interferon Expression and Suppresses Infectious Burse Disease Virus Replication via Targeting SOCS1 and TANK. Frontiers in cellular and infection microbiology 54 29564226
2014 Ubiquitin-specific protease 2b negatively regulates IFN-β production and antiviral activity by targeting TANK-binding kinase 1. Journal of immunology (Baltimore, Md. : 1950) 54 25070846
2019 TANK-binding kinase 1 as a novel therapeutic target for viral diseases. Expert opinion on therapeutic targets 53 30932713
2018 TANK-Binding Kinase 1 (TBK1) Isoforms Negatively Regulate Type I Interferon Induction by Inhibiting TBK1-IRF3 Interaction and IRF3 Phosphorylation. Frontiers in immunology 53 29441066
2015 Spore populations among bulk tank raw milk and dairy powders are significantly different. Journal of dairy science 53 26476952
2012 NEMO binds ubiquitinated TANK-binding kinase 1 (TBK1) to regulate innate immune responses to RNA viruses. PloS one 50 23028469
2015 Encephalomyocarditis Virus 3C Protease Relieves TRAF Family Member-associated NF-κB Activator (TANK) Inhibitory Effect on TRAF6-mediated NF-κB Signaling through Cleavage of TANK. The Journal of biological chemistry 49 26363073
2016 High-density mammalian cell cultures in stirred-tank bioreactor without external pH control. Journal of biotechnology 48 27320019
2009 TANK-binding kinase 1 mediates phosphorylation of insulin receptor at serine residue 994: a potential link between inflammation and insulin resistance. The Journal of endocrinology 46 19251743
2002 Downstream regulator TANK binds to the CD40 recognition site on TRAF3. Structure (London, England : 1993) 45 12005438
2020 Targeting TANK-binding kinase 1 (TBK1) in cancer. Expert opinion on therapeutic targets 43 32962465
2001 Identification and characterization of elevated microbial counts in bulk tank raw milk. Journal of dairy science 43 11210044
1982 Relationships of Bulk Tank Somatic Cell Counts to Prevalence of Intramammary Infection and to Indices of Herd Production 1. Journal of food protection 43 30913711
2006 The TFG protein, involved in oncogenic rearrangements, interacts with TANK and NEMO, two proteins involved in the NF-kappaB pathway. Journal of cellular physiology 42 16547966
2014 Angiogenin reduces immune inflammation via inhibition of TANK-binding kinase 1 expression in human corneal fibroblast cells. Mediators of inflammation 41 24860242
2011 Effects of season, milking routine and cow cleanliness on bacterial and somatic cell counts of bulk tank milk. The Journal of dairy research 40 21843397
2018 Herpes Simplex Virus 1 Inhibits TANK-Binding Kinase 1 through Formation of the Us11-Hsp90 Complex. Journal of virology 38 29743370
2019 Effects of ALS-associated TANK binding kinase 1 mutations on protein-protein interactions and kinase activity. Proceedings of the National Academy of Sciences of the United States of America 37 31748271
2017 Encephalomyocarditis virus 3C protease attenuates type I interferon production through disrupting the TANK-TBK1-IKKε-IRF3 complex. The Biochemical journal 37 28487378
2012 TRAF family member-associated NF-κB activator (TANK) is a negative regulator of osteoclastogenesis and bone formation. The Journal of biological chemistry 37 22773835
2017 The microbiome of bulk tank milk: Characterization and associations with somatic cell count and bacterial count. Journal of dairy science 36 28189327
2017 Assessment of TANK-binding kinase 1 as a therapeutic target in cancer. Journal of cell communication and signaling 36 29218456
2021 TANK-binding kinase 1 (TBK1): An emerging therapeutic target for drug discovery. Drug discovery today 32 34051368
2021 A review on the role of TANK-binding kinase 1 signaling in cancer. International journal of biological macromolecules 31 34111484
2020 Demonstrating the Manufacture of Human CAR-T Cells in an Automated Stirred-Tank Bioreactor. Biotechnology journal 31 32592336
2004 Estimation of septic tank setback distances based on transport of E. coli and F-RNA phages. Environment international 31 14592568
2019 TANK-binding kinase 1 is a mediator of platelet-induced EMT in mammary carcinoma cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 30912981
2015 TANK-binding kinase 1 (TBK1) modulates inflammatory hyperalgesia by regulating MAP kinases and NF-κB dependent genes. Journal of neuroinflammation 30 25997745
2010 Unique differentiation profile of mouse embryonic stem cells in rotary and stirred tank bioreactors. Tissue engineering. Part A 28 20528675
2006 TNFalpha- and IKKbeta-mediated TANK/I-TRAF phosphorylation: implications for interaction with NEMO/IKKgamma and NF-kappaB activation. The Biochemical journal 28 16336209
2022 Oxygen tank for synergistic hypoxia relief to enhance mitochondria-targeted photodynamic therapy. Biomaterials research 25 36138489
1997 Association between management practices, dairy herd characteristics, and somatic cell count of bulk tank milk. Journal of the American Veterinary Medical Association 25 9154205
2020 From Tank to Treatment: Modeling Melanoma in Zebrafish. Cells 24 32455885
2016 Tank-Binding Kinase 1 (TBK1) Gene and Open-Angle Glaucomas (An American Ophthalmological Society Thesis). Transactions of the American Ophthalmological Society 24 27881886
2010 The scaffold protein TANK/I-TRAF inhibits NF-kappaB activation by recruiting polo-like kinase 1. Molecular biology of the cell 24 20484576
2003 Detection and fate of Bacillus anthracis (Sterne) vegetative cells and spores added to bulk tank milk. Journal of food protection 24 14672236
2021 Prevalence and distribution of multilocus sequence types of Staphylococcus aureus isolated from bulk tank milk and cows with mastitis in Pennsylvania. PloS one 23 33711052
2016 Zebrafish STAT6 negatively regulates IFNφ1 production by attenuating the kinase activity of TANK-binding kinase 1. Developmental and comparative immunology 23 27743998
2017 High-performance recombinant protein production with Escherichia coli in continuously operated cascades of stirred-tank reactors. Journal of industrial microbiology & biotechnology 22 28251388
2016 Filling the Tank: Keeping Antitumor T Cells Metabolically Fit for the Long Haul. Cancer immunology research 22 27908931
2014 Genetic obesity alters recruitment of TANK-binding kinase 1 and AKT into hypothalamic lipid rafts domains. Neurochemistry international 22 25447767
2022 Manganese enhances DNA- or RNA-mediated innate immune response by inducing phosphorylation of TANK-binding kinase 1. iScience 21 36325059
2023 Mycoprotein Production by Submerged Fermentation of the Edible Mushroom Pleurotus ostreatus in a Batch Stirred Tank Bioreactor Using Agro-Industrial Hydrolysate. Foods (Basel, Switzerland) 20 37372506
2016 Perfusion Stirred-Tank Bioreactors for 3D Differentiation of Human Neural Stem Cells. Methods in molecular biology (Clifton, N.J.) 20 27032948
2005 Kinetics of batch single cell protein production from rice polishings with Candida utilis in continuously aerated tank reactors. Bioresource technology 20 16226886
2020 Prevalence and characterisation of methicillin-resistant staphylococci from bovine bulk tank milk in England and Wales. Journal of global antimicrobial resistance 19 32006753
2020 TANK-binding kinase 1 mediates osteoclast differentiation by regulating NF-κB, MAPK and Akt signaling pathways. Immunology and cell biology 18 32896936
2015 Production of halophilic proteins using Haloferax volcanii H1895 in a stirred-tank bioreactor. Applied microbiology and biotechnology 18 26428236
2011 Tank-treading and tumbling frequencies of capsules and red blood cells. Physical review. E, Statistical, nonlinear, and soft matter physics 18 21599293
2010 Mycobacterium avium subsp. paratuberculosis detection in individual and bulk tank milk samples from bovine herds and caprine flocks. Foodborne pathogens and disease 18 19911881
2022 Therapeutic targeting of TANK-binding kinase signaling towards anticancer drug development: Challenges and opportunities. International journal of biological macromolecules 17 35358582
2013 Chryseobacterium angstadtii sp. nov., isolated from a newt tank. International journal of systematic and evolutionary microbiology 17 23996834
2011 Inducible SUMO modification of TANK alleviates its repression of TLR7 signalling. EMBO reports 17 21212807
2021 Longitudinal Study of the Bulk Tank Milk Microbiota Reveals Major Temporal Shifts in Composition. Frontiers in microbiology 16 33708181
2016 TANK-binding kinase-1 broadly affects oyster immune response to bacteria and viruses. Fish & shellfish immunology 16 27422757
2021 Dual Regulation of Tank Binding Kinase 1 by BRG1 in Hepatocytes Contributes to Reactive Oxygen Species Production. Frontiers in cell and developmental biology 15 34660604
2017 Molecular basis for TANK recognition by TRAF1 revealed by the crystal structure of TRAF1/TANK complex. FEBS letters 15 28155233
2012 OxLDL inhibits LPS-induced IFNβ expression by Pellino3- and IRAK1/4-dependent modification of TANK. Cellular signalling 15 22330071
2012 TRAF family member-associated NF-κB activator (TANK) induced by RANKL negatively regulates osteoclasts survival and function. International journal of biological sciences 15 23139637
2012 TRAF family member-associated NF-kappa B activator (TANK) expression increases in injured sensory neurons and is transcriptionally regulated by Sox11. Neuroscience 15 23201825
2024 Targeting TANK-binding kinase 1 attenuates painful diabetic neuropathy via inhibiting microglia pyroptosis. Cell communication and signaling : CCS 14 39030571
2022 Enabling Allogeneic T Cell-Based Therapies: Scalable Stirred-Tank Bioreactor Mediated Manufacturing. Frontiers in medical technology 14 35707712
2022 PLK1 protects intestinal barrier function during sepsis by targeting mitochondrial dynamics through TANK-NF-κB signalling. Molecular medicine (Cambridge, Mass.) 14 36581806
2020 Fate and Fathead Minnow Embryotoxicity of Weathering Crude Oil in a Pilot-Scale Spill Tank. Environmental toxicology and chemistry 14 33017057
2019 The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking: A Translational Study. Cerebral cortex (New York, N.Y. : 1991) 14 30721969
2009 Relationship between somatic cell count, polymorphonuclear leucocyte count and quality parameters in bovine bulk tank milk. The Journal of dairy research 14 19281626
2024 Lumpy skin disease virus ORF127 protein suppresses type I interferon responses by inhibiting K63-linked ubiquitination of tank binding kinase 1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 13 38329325
2019 The transient expression of CHIKV VLP in large stirred tank bioreactors. Cytotechnology 13 31560090
2012 Somatic cells count in cow's bulk tank milk. The Journal of veterinary medical science 13 22230979
2021 Human Metapneumovirus Induces IRF1 via TANK-Binding Kinase 1 and Type I IFN. Frontiers in immunology 12 34248923
2019 Cell Metabolism Control Through O-GlcNAcylation of STAT5: A Full or Empty Fuel Tank Makes a Big Difference for Cancer Cell Growth and Survival. International journal of molecular sciences 12 30818760
2018 Phosphorylation-induced changes in the energetic frustration in human Tank binding kinase 1. Journal of theoretical biology 12 29653159
2010 TACI induces cIAP1-mediated ubiquitination of NIK by TRAF2 and TANK to limit non-canonical NF-kappaB signaling. Journal of receptor and signal transduction research 12 20184394

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