3brv › Citations

Structure of a NEMO/IKK-associating domain reveals architecture of the interaction site.

Rushe M, Silvian L, Bixler S, Chen LL, Cheung A, Bowes S, Cuervo H, Berkowitz S, Zheng T, Guckian K, Pellegrini M, Lugovskoy A
Structure 16 798-808 (2008)
Cited: 97 times
EuropePMC logo PMID: 18462684

Abstract

The phosphorylation of IkappaB by the IKK complex targets it for degradation and releases NF-kappaB for translocation into the nucleus to initiate the inflammatory response, cell proliferation, or cell differentiation. The IKK complex is composed of the catalytic IKKalpha/beta kinases and a regulatory protein, NF-kappaB essential modulator (NEMO; IKKgamma). NEMO associates with the unphosphorylated IKK kinase C termini and activates the IKK complex's catalytic activity. However, detailed structural information about the NEMO/IKK interaction is lacking. In this study, we have identified the minimal requirements for NEMO and IKK kinase association using a variety of biophysical techniques and have solved two crystal structures of the minimal NEMO/IKK kinase associating domains. We demonstrate that the NEMO core domain is a dimer that binds two IKK fragments and identify energetic hot spots that can be exploited to inhibit IKK complex formation with a therapeutic agent.

Reviews - 3brv mentioned but not cited (4)

  1. NF-κB regulation: lessons from structures. Ghosh G, Wang VY, Huang DB, Fusco A. Immunol. Rev. 246 36-58 (2012)
  2. Scaffold proteins as dynamic integrators of biological processes. DiRusso CJ, Dashtiahangar M, Gilmore TD. J Biol Chem 298 102628 (2022)
  3. A Comprehensive Review on Cannabis sativa Ethnobotany, Phytochemistry, Molecular Docking and Biological Activities. Hourfane S, Mechqoq H, Bekkali AY, Rocha JM, El Aouad N. Plants (Basel) 12 1245 (2023)
  4. Pharmacological Properties, Molecular Mechanisms, and Pharmaceutical Development of Asiatic Acid: A Pentacyclic Triterpenoid of Therapeutic Promise. Nagoor Meeran MF, Goyal SN, Suchal K, Sharma C, Patil CR, Ojha SK. Front Pharmacol 9 892 (2018)

Articles - 3brv mentioned but not cited (28)

  1. Structural and evolutionary classification of Type II restriction enzymes based on theoretical and experimental analyses. Orlowski J, Bujnicki JM. Nucleic Acids Res. 36 3552-3569 (2008)
  2. Inhibition of the NEMO/IKKβ association complex formation, a novel mechanism associated with the NF-κB activation suppression by Withania somnifera's key metabolite withaferin A. Grover A, Shandilya A, Punetha A, Bisaria VS, Sundar D. BMC Genomics 11 Suppl 4 S25 (2010)
  3. Relationship between hot spot residues and ligand binding hot spots in protein-protein interfaces. Zerbe BS, Hall DR, Vajda S, Whitty A, Kozakov D. J Chem Inf Model 52 2236-2244 (2012)
  4. Comprehensive experimental and computational analysis of binding energy hot spots at the NF-κB essential modulator/IKKβ protein-protein interface. Golden MS, Cote SM, Sayeg M, Zerbe BS, Villar EA, Beglov D, Sazinsky SL, Georgiadis RM, Vajda S, Kozakov D, Whitty A. J. Am. Chem. Soc. 135 6242-6256 (2013)
  5. Pentacyclic Triterpenoids Inhibit IKKβ Mediated Activation of NF-κB Pathway: In Silico and In Vitro Evidences. Patil KR, Mohapatra P, Patel HM, Goyal SN, Ojha S, Kundu CN, Patil CR. PLoS ONE 10 e0125709 (2015)
  6. Structural attributes for the recognition of weak and anomalous regions in coiled-coils of myosins and other motor proteins. Sunitha MS, Nair AG, Charya A, Jadhav K, Mukhopadhyay S, Sowdhamini R. BMC Res Notes 5 530 (2012)
  7. Identification of human IKK-2 inhibitors of natural origin (part I): modeling of the IKK-2 kinase domain, virtual screening and activity assays. Sala E, Guasch L, Iwaszkiewicz J, Mulero M, Salvadó MJ, Pinent M, Zoete V, Grosdidier A, Garcia-Vallvé S, Michielin O, Pujadas G. PLoS ONE 6 e16903 (2011)
  8. Highly precise protein-protein interaction prediction based on consensus between template-based and de novo docking methods. Ohue M, Matsuzaki Y, Shimoda T, Ishida T, Akiyama Y. BMC Proc 7 S6 (2013)
  9. Polyubiquitin Drives the Molecular Interactions of the NF-κB Essential Modulator (NEMO) by Allosteric Regulation. Catici DA, Horne JE, Cooper GE, Pudney CR. J. Biol. Chem. 290 14130-14139 (2015)
  10. Protein engineering of the N-terminus of NEMO: structure stabilization and rescue of IKKβ binding. Guo B, Audu CO, Cochran JC, Mierke DF, Pellegrini M. Biochemistry 53 6776-6785 (2014)
  11. A Synthetic Loop Replacement Peptide That Blocks Canonical NF-κB Signaling. Bruno PA, Morriss-Andrews A, Henderson AR, Brooks CL, Mapp AK. Angew. Chem. Int. Ed. Engl. 55 14997-15001 (2016)
  12. Development of novel NEMO-binding domain mimetics for inhibiting IKK/NF-κB activation. Zhao J, Zhang L, Mu X, Doebelin C, Nguyen W, Wallace C, Reay DP, McGowan SJ, Corbo L, Clemens PR, Wilson GM, Watkins SC, Solt LA, Cameron MD, Huard J, Niedernhofer LJ, Kamenecka TM, Robbins PD. PLoS Biol. 16 e2004663 (2018)
  13. Tetrazoles via Multicomponent Reactions. Neochoritis CG, Zhao T, Dömling A. Chem. Rev. 119 1970-2042 (2019)
  14. Disulfide-mediated stabilization of the IκB kinase binding domain of NF-κB essential modulator (NEMO). Zhou L, Yeo AT, Ballarano C, Weber U, Allen KN, Gilmore TD, Whitty A. Biochemistry 53 7929-7944 (2014)
  15. S-allyl cysteine reduces osteoarthritis pathology in the tert-butyl hydroperoxide-treated chondrocytes and the destabilization of the medial meniscus model mice via the Nrf2 signaling pathway. Shao Z, Pan Z, Lin J, Zhao Q, Wang Y, Ni L, Feng S, Tian N, Wu Y, Sun L, Gao W, Zhou Y, Zhang X, Wang X. Aging (Albany NY) 12 19254-19272 (2020)
  16. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, Dutta M, Ghosh AS, Oda M, Venkatramani R, Rao BJ, Dandekar AM, Goñi FM. F1000Res 2 286 (2013)
  17. Super-resolution microscopy reveals a preformed NEMO lattice structure that is collapsed in incontinentia pigmenti. Scholefield J, Henriques R, Savulescu AF, Fontan E, Boucharlat A, Laplantine E, Smahi A, Israël A, Agou F, Mhlanga MM. Nat Commun 7 12629 (2016)
  18. A Thermodynamic Model for Interpreting Tryptophan Excitation-Energy-Dependent Fluorescence Spectra Provides Insight Into Protein Conformational Sampling and Stability. Kwok A, Camacho IS, Winter S, Knight M, Meade RM, Van der Kamp MW, Turner A, O'Hara J, Mason JM, Jones AR, Arcus VL, Pudney CR. Front Mol Biosci 8 778244 (2021)
  19. Carica Papaya Reduces High Fat Diet and Streptozotocin-Induced Development of Inflammation in Adipocyte via IL-1β/IL-6/TNF-α Mediated Signaling Mechanisms in Type-2 Diabetic Rats. Rebecca Roy J, Janaki CS, Jayaraman S, Periyasamy V, Balaji T, Vijayamalathi M, Veeraraghavan VP, Krishnamoorthy K, Prasad M. Curr Issues Mol Biol 45 852-884 (2023)
  20. Cytotoxicity and Pro-Apoptotic, Antioxidant and Anti-Inflammatory Activities of Geopropolis Produced by the Stingless Bee Melipona fasciculata Smith. Barboza JR, Pereira FAN, Fernandes RA, Vasconcelos CC, Cartágenes MDSS, Oliveira Lopes AJ, Melo AC, Guimarães IDS, Rocha CQD, Ribeiro MNS. Biology (Basel) 9 (2020)
  21. Mechanistic insights into the activation of the IKK kinase complex by the Kaposi's sarcoma herpes virus oncoprotein vFLIP. Bagnéris C, Senthil Kumar SL, Baratchian M, Britt HM, Assafa TE, Thalassinos K, Collins MK, Barrett TE. J Biol Chem 298 102012 (2022)
  22. Molecular mechanism underlying the anti-inflammatory effects of volatile components of Ligularia fischeri (Ledeb) Turcz based on network pharmacology. Huang X, Gao Y, Xu F, Fan D, Liang Y, Wang X, Wu H. BMC Complement Med Ther 20 109 (2020)
  23. Novel Isoquinoline Alkaloid Litcubanine A - A Potential Anti-Inflammatory Candidate. Xia H, Liu Y, Xia G, Liu Y, Lin S, Guo L. Front Immunol 12 685556 (2021)
  24. Phenotypic Screening of Molecular Docking Enriched Chemical Libraries from Targets Identified in Ischemic Stroke Genome Data by Network-Based Method. Peng X, Xue DJ. J Healthc Eng 2021 9999340 (2021)
  25. Production, Crystallization, and Structure Determination of the IKK-binding Domain of NEMO. Barczewski AH, Ragusa MJ, Mierke DF, Pellegrini M. J Vis Exp (2019)
  26. The IKK-binding domain of NEMO is an irregular coiled coil with a dynamic binding interface. Barczewski AH, Ragusa MJ, Mierke DF, Pellegrini M. Sci Rep 9 2950 (2019)
  27. Utilizing molecular docking and cell validation to explore the potential mechanisms of lupenone attenuating the inflammatory response via NF-κB pathway. Wang X, Liu M, Li X, Zhang M, Xu F, Liu H, Wu H. Sci Rep 14 625 (2024)
  28. Voacanga globosa Spirobisindole Alkaloids Exert Antiviral Activity in HIV Latently Infected Cell Lines by Targeting the NF-kB Cascade: In Vitro and In Silico Investigations. de Jesus MSM, Macabeo APG, Ramos JDA, de Leon VNO, Asamitsu K, Okamoto T. Molecules 27 1078 (2022)


Reviews citing this publication (17)

  1. Molecular basis of NF-κB signaling. Napetschnig J, Wu H. Annu Rev Biophys 42 443-468 (2013)
  2. The IKK complex, a central regulator of NF-kappaB activation. Israël A. Cold Spring Harb Perspect Biol 2 a000158 (2010)
  3. The IκB kinase complex in NF-κB regulation and beyond. Hinz M, Scheidereit C. EMBO Rep. 15 46-61 (2014)
  4. Linear polyubiquitination: a new regulator of NF-kappaB activation. Iwai K, Tokunaga F. EMBO Rep. 10 706-713 (2009)
  5. Nuclear initiated NF-κB signaling: NEMO and ATM take center stage. Miyamoto S. Cell Res. 21 116-130 (2011)
  6. IKK biology. Liu F, Xia Y, Parker AS, Verma IM. Immunol. Rev. 246 239-253 (2012)
  7. The IkappaB kinase complex: master regulator of NF-kappaB signaling. Solt LA, May MJ. Immunol. Res. 42 3-18 (2008)
  8. NF-kappaB signaling: a tale of two pathways in skeletal myogenesis. Bakkar N, Guttridge DC. Physiol. Rev. 90 495-511 (2010)
  9. The pivotal role of TBK1 in inflammatory responses mediated by macrophages. Yu T, Yi YS, Yang Y, Oh J, Jeong D, Cho JY. Mediators Inflamm. 2012 979105 (2012)
  10. Structural studies of NF-κB signaling. Zheng C, Yin Q, Wu H. Cell Res. 21 183-195 (2011)
  11. Structural basis of signal transduction in the TNF receptor superfamily. Li J, Yin Q, Wu H. Adv. Immunol. 119 135-153 (2013)
  12. Inhibitory kappa B Kinases as targets for pharmacological regulation. Gamble C, McIntosh K, Scott R, Ho KH, Plevin R, Paul A. Br. J. Pharmacol. 165 802-819 (2012)
  13. A structural guide to proteins of the NF-kappaB signaling module. Huxford T, Ghosh G. Cold Spring Harb Perspect Biol 1 a000075 (2009)
  14. Structural insights into the assembly of large oligomeric signalosomes in the Toll-like receptor-interleukin-1 receptor superfamily. Ferrao R, Li J, Bergamin E, Wu H. Sci Signal 5 re3 (2012)
  15. Cell penetrating peptide inhibitors of nuclear factor-kappa B. Orange JS, May MJ. Cell. Mol. Life Sci. 65 3564-3591 (2008)
  16. Significance of optineurin mutations in glaucoma and other diseases. Minegishi Y, Nakayama M, Iejima D, Kawase K, Iwata T. Prog Retin Eye Res 55 149-181 (2016)
  17. Targeting NF-κB Signaling for Multiple Myeloma. Wong AH, Shin EM, Tergaonkar V, Chng WJ. Cancers (Basel) 12 (2020)

Articles citing this publication (48)

  1. Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation. Rahighi S, Ikeda F, Kawasaki M, Akutsu M, Suzuki N, Kato R, Kensche T, Uejima T, Bloor S, Komander D, Randow F, Wakatsuki S, Dikic I. Cell 136 1098-1109 (2009)
  2. A nuclear poly(ADP-ribose)-dependent signalosome confers DNA damage-induced IkappaB kinase activation. Stilmann M, Hinz M, Arslan SC, Zimmer A, Schreiber V, Scheidereit C. Mol. Cell 36 365-378 (2009)
  3. NEMO specifically recognizes K63-linked poly-ubiquitin chains through a new bipartite ubiquitin-binding domain. Laplantine E, Fontan E, Chiaravalli J, Lopez T, Lakisic G, Véron M, Agou F, Israël A. EMBO J. 28 2885-2895 (2009)
  4. Crystal structure of inhibitor of κB kinase β. Xu G, Lo YC, Li Q, Napolitano G, Wu X, Jiang X, Dreano M, Karin M, Wu H. Nature 472 325-330 (2011)
  5. Crystal structure and mechanism of activation of TANK-binding kinase 1. Larabi A, Devos JM, Ng SL, Nanao MH, Round A, Maniatis T, Panne D. Cell Rep 3 734-746 (2013)
  6. A structural basis for IκB kinase 2 activation via oligomerization-dependent trans auto-phosphorylation. Polley S, Huang DB, Hauenstein AV, Fusco AJ, Zhong X, Vu D, Schröfelbauer B, Kim Y, Hoffmann A, Verma IM, Ghosh G, Huxford T. PLoS Biol. 11 e1001581 (2013)
  7. Crystal structure of the NEMO ubiquitin-binding domain in complex with Lys 63-linked di-ubiquitin. Yoshikawa A, Sato Y, Yamashita M, Mimura H, Yamagata A, Fukai S. FEBS Lett. 583 3317-3322 (2009)
  8. NEMO oligomerization and its ubiquitin-binding properties. Ivins FJ, Montgomery MG, Smith SJ, Morris-Davies AC, Taylor IA, Rittinger K. Biochem. J. 421 243-251 (2009)
  9. Crystal structure of a human IκB kinase β asymmetric dimer. Liu S, Misquitta YR, Olland A, Johnson MA, Kelleher KS, Kriz R, Lin LL, Stahl M, Mosyak L. J. Biol. Chem. 288 22758-22767 (2013)
  10. DARPin-assisted crystallography of the CC2-LZ domain of NEMO reveals a coupling between dimerization and ubiquitin binding. Grubisha O, Kaminska M, Duquerroy S, Fontan E, Cordier F, Haouz A, Raynal B, Chiaravalli J, Delepierre M, Israël A, Véron M, Agou F. J. Mol. Biol. 395 89-104 (2010)
  11. Novel insights into the cellular mechanisms of the anti-inflammatory effects of NF-kappaB essential modulator binding domain peptides. Baima ET, Guzova JA, Mathialagan S, Nagiec EE, Hardy MM, Song LR, Bonar SL, Weinberg RA, Selness SR, Woodard SS, Chrencik J, Hood WF, Schindler JF, Kishore N, Mbalaviele G. J. Biol. Chem. 285 13498-13506 (2010)
  12. NEMO-binding domains of both IKKalpha and IKKbeta regulate IkappaB kinase complex assembly and classical NF-kappaB activation. Solt LA, Madge LA, May MJ. J. Biol. Chem. 284 27596-27608 (2009)
  13. IκB kinase γ/nuclear factor-κB-essential modulator (IKKγ/NEMO) facilitates RhoA GTPase activation, which, in turn, activates Rho-associated KINASE (ROCK) to phosphorylate IKKβ in response to transforming growth factor (TGF)-β1. Kim HJ, Kim JG, Moon MY, Park SH, Park JB. J. Biol. Chem. 289 1429-1440 (2014)
  14. Structural insights into the interaction and disease mechanism of neurodegenerative disease-associated optineurin and TBK1 proteins. Li F, Xie X, Wang Y, Liu J, Cheng X, Guo Y, Gong Y, Hu S, Pan L. Nat Commun 7 12708 (2016)
  15. Identification of a new NEMO/TRAF6 interface affected in incontinentia pigmenti pathology. Gautheron J, Pescatore A, Fusco F, Esposito E, Yamaoka S, Agou F, Ursini MV, Courtois G. Hum. Mol. Genet. 19 3138-3149 (2010)
  16. NBD delivery improves the disease phenotype of the golden retriever model of Duchenne muscular dystrophy. Kornegay JN, Peterson JM, Bogan DJ, Kline W, Bogan JR, Dow JL, Fan Z, Wang J, Ahn M, Zhu H, Styner M, Guttridge DC. Skelet Muscle 4 18 (2014)
  17. Human kinome drug discovery and the emerging importance of atypical allosteric inhibitors. Eglen RM, Reisine T. Expert Opin Drug Discov 5 277-290 (2010)
  18. A homogeneous time-resolved fluorescence-based high-throughput screening system for discovery of inhibitors of IKKbeta-NEMO interaction. Gotoh Y, Nagata H, Kase H, Shimonishi M, Ido M. Anal. Biochem. 405 19-27 (2010)
  19. Probing the Solution Structure of IκB Kinase (IKK) Subunit γ and Its Interaction with Kaposi Sarcoma-associated Herpes Virus Flice-interacting Protein and IKK Subunit β by EPR Spectroscopy. Bagnéris C, Rogala KB, Baratchian M, Zamfir V, Kunze MB, Dagless S, Pirker KF, Collins MK, Hall BA, Barrett TE, Kay CW. J. Biol. Chem. 290 16539-16549 (2015)
  20. Evidence that the kinase-truncated c-Src regulates NF-κB signaling by targeting NEMO. Dai S, Abu-Amer W, Karuppaiah K, Abu-Amer Y. J. Cell. Biochem. 112 2463-2470 (2011)
  21. Inhibition of Canonical NF-κB Signaling by a Small Molecule Targeting NEMO-Ubiquitin Interaction. Vincendeau M, Hadian K, Messias AC, Brenke JK, Halander J, Griesbach R, Greczmiel U, Bertossi A, Stehle R, Nagel D, Demski K, Velvarska H, Niessing D, Geerlof A, Sattler M, Krappmann D. Sci Rep 6 18934 (2016)
  22. Mutation of nonessential cysteines shows that the NF-κB essential modulator forms a constitutive noncovalent dimer that binds IκB kinase-β with high affinity. Cote SM, Gilmore TD, Shaffer R, Weber U, Bollam R, Golden MS, Glover K, Herscovitch M, Ennis T, Allen KN, Whitty A. Biochemistry 52 9141-9154 (2013)
  23. Novel Phosphorylations of IKKγ/NEMO. Lee SH, Toth Z, Wong LY, Brulois K, Nguyen J, Lee JY, Zandi E, Jung JU. MBio 3 e00411-12 (2012)
  24. Regulation of I(kappa)B kinase complex by phosphorylation of (gamma)-binding domain of I(kappa)B kinase (beta) by Polo-like kinase 1. Higashimoto T, Chan N, Lee YK, Zandi E. J. Biol. Chem. 283 35354-35367 (2008)
  25. A Central Region of NF-κB Essential Modulator Is Required for IKKβ-Induced Conformational Change and for Signal Propagation. Shaffer R, DeMaria AM, Kagermazova L, Liu Y, Babaei M, Caban-Penix S, Cervantes A, Jehle S, Makowski L, Gilmore TD, Whitty A, Allen KN. Biochemistry 58 2906-2920 (2019)
  26. Binding mode analysis of zerumbone to key signal proteins in the tumor necrosis factor pathway. Fatima A, Abdul AB, Abdullah R, Karjiban RA, Lee VS. Int J Mol Sci 16 2747-2766 (2015)
  27. COMMD7 as a novel NEMO interacting protein involved in the termination of NF-κB signaling. Esposito E, Napolitano G, Pescatore A, Calculli G, Incoronato MR, Leonardi A, Ursini MV. J. Cell. Physiol. 231 152-161 (2016)
  28. Enhancing the Cell Permeability and Metabolic Stability of Peptidyl Drugs by Reversible Bicyclization. Qian Z, Rhodes CA, McCroskey LC, Wen J, Appiah-Kubi G, Wang DJ, Guttridge DC, Pei D. Angew. Chem. Int. Ed. Engl. 56 1525-1529 (2017)
  29. Evidence for M1-Linked Polyubiquitin-Mediated Conformational Change in NEMO. Hauenstein AV, Xu G, Kabaleeswaran V, Wu H. J. Mol. Biol. 429 3793-3800 (2017)
  30. Inflammatory osteolysis is regulated by site-specific ISGylation of the scaffold protein NEMO. Adapala NS, Swarnkar G, Arra M, Shen J, Mbalaviele G, Ke K, Abu-Amer Y. Elife 9 (2020)
  31. Structure of the extracellular domains of human and Xenopus Fn14: implications in the evolution of TWEAK and Fn14 interactions. Pellegrini M, Willen L, Perroud M, Krushinskie D, Strauch K, Cuervo H, Day ES, Schneider P, Zheng TS. FEBS J. 280 1818-1829 (2013)
  32. Expression, purification and functional characterization of IkappaB kinase-2 (IKK-2) mutants. Mathialagan S, Poda GI, Kurumbail RG, Selness SR, Hall T, Reitz BA, Weinberg RA, Kishore N, Mbalaviele G. Protein Expr. Purif. 72 254-261 (2010)
  33. Lack of interaction between NEMO and SHARPIN impairs linear ubiquitination and NF-κB activation and leads to incontinentia pigmenti. Bal E, Laplantine E, Hamel Y, Dubosclard V, Boisson B, Pescatore A, Picard C, Hadj-Rabia S, Royer G, Steffann J, Bonnefont JP, Ursini VM, Vabres P, Munnich A, Casanova JL, Bodemer C, Weil R, Agou F, Smahi A. J. Allergy Clin. Immunol. 140 1671-1682.e2 (2017)
  34. RhoA GTPase oxidation stimulates cell proliferation via nuclear factor-κB activation. Kim JG, Kwon HJ, Wu G, Park Y, Lee JY, Kim J, Kim SC, Choe M, Kang SG, Seo GY, Kim PH, Park JB. Free Radic. Biol. Med. 103 57-68 (2017)
  35. Cell-Permeable Bicyclic Peptidyl Inhibitors against NEMO-IκB Kinase Interaction Directly from a Combinatorial Library. Rhodes CA, Dougherty PG, Cooper JK, Qian Z, Lindert S, Wang QE, Pei D. J. Am. Chem. Soc. 140 12102-12110 (2018)
  36. Functional Evaluation of an IKBKG Variant Suspected to Cause Immunodeficiency Without Ectodermal Dysplasia. Frans G, van der Werff Ten Bosch J, Moens L, Gijsbers R, Changi-Ashtiani M, Rokni-Zadeh H, Shahrooei M, Wuyts G, Meyts I, Bossuyt X. J. Clin. Immunol. 37 801-810 (2017)
  37. Mechanism of vaccinia viral protein B14-mediated inhibition of IκB kinase β activation. Tang Q, Chakraborty S, Xu G. J. Biol. Chem. 293 10344-10352 (2018)
  38. N4BP1 negatively regulates NF-κB by binding and inhibiting NEMO oligomerization. Shi H, Sun L, Wang Y, Liu A, Zhan X, Li X, Tang M, Anderton P, Hildebrand S, Quan J, Ludwig S, Moresco EMY, Beutler B. Nat Commun 12 1379 (2021)
  39. Structurally plastic NEMO and oligomerization prone IKK2 subunits define the behavior of human IKK2:NEMO complexes in solution. Ko MS, Biswas T, Mulero MC, Bobkov AA, Ghosh G, Huxford T. Biochim Biophys Acta Proteins Proteom 1868 140526 (2020)
  40. Tyr42 phosphorylation of RhoA GTPase promotes tumorigenesis through nuclear factor (NF)-κB. Kim JG, Choi KC, Hong CW, Park HS, Choi EK, Kim YS, Park JB. Free Radic. Biol. Med. 112 69-83 (2017)
  41. A conserved core region of the scaffold NEMO is essential for signal-induced conformational change and liquid-liquid phase separation. DiRusso CJ, DeMaria AM, Wong J, Wang W, Jordanides JJ, Whitty A, Allen KN, Gilmore TD. J Biol Chem 299 105396 (2023)
  42. Characterization of a small-molecule inhibitor targeting NEMO/IKKβ to suppress colorectal cancer growth. Yu Z, Gao J, Zhang X, Peng Y, Wei W, Xu J, Li Z, Wang C, Zhou M, Tian X, Feng L, Huo X, Liu M, Ye M, Guo DA, Ma X. Signal Transduct Target Ther 7 71 (2022)
  43. Damaged mitochondria recruit the effector NEMO to activate NF-κB signaling. Harding O, Holzer E, Riley JF, Martens S, Holzbaur ELF. Mol Cell 83 3188-3204.e7 (2023)
  44. LCC-09, a Novel Salicylanilide Derivative, Exerts Anti-Inflammatory Effect in Vascular Endothelial Cells. Angom RS, Zhu J, Wu ATH, Sumitra MR, Pham V, Dutta S, Wang E, Madamsetty VS, Perez-Cordero GD, Huang HS, Mukhopadhyay D, Wang Y. J Inflamm Res 14 4551-4565 (2021)
  45. Low Density Granulocytes and Dysregulated Neutrophils Driving Autoinflammatory Manifestations in NEMO Deficiency. Surucu Yilmaz N, Bilgic Eltan S, Kayaoglu B, Geckin B, Heredia RJ, Sefer AP, Kiykim A, Nain E, Kasap N, Dogru O, Yucelten AD, Cinel L, Karasu G, Yesilipek A, Sozeri B, Kaya GG, Yilmaz IC, Baydemir I, Aydin Y, Cansen Kahraman D, Haimel M, Boztug K, Karakoc-Aydiner E, Gursel I, Ozen A, Baris S, Gursel M. J Clin Immunol 42 582-596 (2022)
  46. Molecular Insights Into Withaferin-A-Induced Senescence: Bioinformatics and Experimental Evidence to the Role of NFκB and CARF. Bhargava P, Malik V, Liu Y, Ryu J, Kaul SC, Sundar D, Wadhwa R. J. Gerontol. A Biol. Sci. Med. Sci. 74 183-191 (2019)
  47. Regulatory subunit NEMO promotes polyubiquitin-dependent induction of NF-κB through a targetable second interaction with upstream activator IKK2. Ko MS, Cohen SN, Polley S, Mahata SK, Biswas T, Huxford T, Ghosh G. J Biol Chem 298 101864 (2022)
  48. Structural and functional characterization of NEMO cleavage by SARS-CoV-2 3CLpro. Hameedi MA, T Prates E, Garvin MR, Mathews II, Amos BK, Demerdash O, Bechthold M, Iyer M, Rahighi S, Kneller DW, Kovalevsky A, Irle S, Vuong VQ, Mitchell JC, Labbe A, Galanie S, Wakatsuki S, Jacobson D. Nat Commun 13 5285 (2022)


Quick links