Skip to main content

NF-κB Family

  • 121 Accesses

Synonyms

Nuclear factor-kappa-B; Nuclear factor of kappa light polypeptide gene enhancer in B cells

List of Discussed NF-κB Family Members and Regulatory Molecules

NFκB1: p105, p50, KBF1, EBP-1

RelA: p65, NFKB3

RelB: I-REL

REL: c-Rel

NFκB2: p100, p52; LYT10

Bcl-3: BCL4, D19S37

NFKBIA: IκBα, IKBA, MAD-3, NFKBI

NFKBIB: IκBβ, IKBB, TRIP9

NFKBIE: IκBε, IKBE

NFKBIZ: IκBζ, IKBZ, INAP, MAIL

CHUK: IKKα, IKBKA, IKK1, IKKA, NFKBIKA, TCF16

IKBKB: IKKβ, IKK2, IKKB, NFKBIKB

IKBKG: IKKγ, NEMO, AMCBX1, FIP-3, FIP3, Fip3p, IP, IP1, IP2, IPD2, IKKAP1, IKKG

IKBKE: IKKε, IKKE, IKKI

MAP3K14: NIK, HS, HSNIK

TNFAIP3: A20, OTUD7C, TNFA1P2

OTUD7B: CEZANNE

CYLD: HSPC057, CDMT, CYLD1, CYLDI, EAC, MFT1, SBS, TEM, USPL2

Historical Background: Discovery and Structure

NF-κB (nuclear factor-kappa-light-chain-enhancer of activated B cells) is a collective term for a family of transcription factors. NF-κB has a complex regulation, modulates the expression of a wide set of genes, both by promoting and by suppressing...

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-3-319-67199-4_220
  • Chapter length: 10 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   5,499.99
Price excludes VAT (USA)
  • ISBN: 978-3-319-67199-4
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Hardcover Book
USD   7,499.99
Price excludes VAT (USA)
NF-κB Family, Fig. 1
NF-κB Family, Fig. 2

References

  • Beg AA, Sha WC, Bronson RT, Ghosh S, Baltimore D. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B. Nature. 1995;376:167–70.

    CrossRef  CAS  PubMed  Google Scholar 

  • Caamaño JH, Rizzo CA, Durham SK, Barton DS, Raventós-Suárez C, Snapper CM, Bravo R. Nuclear factor (NF)-kappa B2 (p100/p52) is required for normal splenic microarchitecture and B cell-mediated immune responses. J Exp Med. 1998;187:185–96.

    PubMed  PubMed Central  CrossRef  Google Scholar 

  • Collins T, Cybulsky MI. NF-kappaB: pivotal mediator or innocent bystander in atherogenesis? J Clin Invest. 2001;107:255–64.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Ghosh S, Hayden MS. New regulators of NF-kappaB in inflammation. Nat Rev Immunol. 2008;8:837–48.

    CrossRef  CAS  PubMed  Google Scholar 

  • Gilmore TD. Introduction to NF-kappaB: players, pathways, perspectives. Oncogene. 2006;25:6680–4.

    CrossRef  CAS  PubMed  Google Scholar 

  • González-Guerrero C, Ocaña-Salceda C, Berzal S, Carrasco S, Fernández-Fernández B, Cannata-Ortiz P, Egido J, Ortiz A, Ramos AM. Calcineurin inhibitors recruit protein kinases JAK2 and JNK, TLR signaling and the UPR to activate NF-κB-mediated inflammatory responses in kidney tubular cells. Toxicol Appl Pharmacol. 2013;272(3):825–41.

    CrossRef  CAS  PubMed  Google Scholar 

  • Haas AL. Linear polyubiquitylation: the missing link in NF-kappaB signalling. Nat Cell Biol. 2009;11:116–8.

    CrossRef  CAS  PubMed  Google Scholar 

  • Harris J, Olière S, Sharma S, Sun Q, Lin R, Hiscott J, Grandvaux N. Nuclear accumulation of cRel following C-terminal phosphorylation by TBK1/IKKepsilon. J Immunol. 2006;177:2527–35.

    CrossRef  CAS  PubMed  Google Scholar 

  • Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev. 2004;18:2195–224.

    CrossRef  CAS  PubMed  Google Scholar 

  • He WA, Berardi E, Cardillo VM, Acharyya S, Aulino P, Thomas-Ahner J, Wang J, Bloomston M, Muscarella P, Nau P, Shah N, Butchbach ME, Ladner K, Adamo S, Rudnicki MA, Keller C, Coletti D, Montanaro F, Guttridge DC. NF-κB-mediated Pax7 dysregulation in the muscle microenvironment promotes cancer cachexia. J Clin Invest. 2013;123(11):4821–35.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Hoffmann A, Levchenko A, Scott ML, Baltimore D. The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation. Science. 2002;298:1241–5.

    CrossRef  CAS  PubMed  Google Scholar 

  • Hu H, Brittain GC, Chang JH, Puebla-Osorio N, Jin J, Zal A, Xiao Y, Cheng X, Chang M, Fu YX, Zal T, Zhu C, Sun SC. OTUD7B controls non-canonical NF-κB activation through deubiquitination of TRAF3. Nature. 2013;494(7437):371–4.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Karin M, Delhase M. The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling. Semin Immunol. 2000;12:85–98.

    CrossRef  CAS  PubMed  Google Scholar 

  • Kellogg RA, Tay S. Noise facilitates transcriptional control under dynamic inputs. Cell. 2015;160(3):381–92.

    CrossRef  CAS  PubMed  Google Scholar 

  • Korc M. RelA: a tale of a stitch in time. J Clin Invest. 2016;126(8):2799–801.

    PubMed  PubMed Central  CrossRef  Google Scholar 

  • Kumar A, Takada Y, Boriek AM, Aggarwal BB. Nuclear factor-kappaB: its role in health and disease. J Mol Med. 2004;82:434–48.

    CrossRef  CAS  PubMed  Google Scholar 

  • Li Q, Verma IM. NF-kappaB regulation in the immune system. Nat Rev Immunol. 2002;2:725–34.

    CrossRef  CAS  PubMed  Google Scholar 

  • Li ZW, Chu W, Hu Y, Delhase M, Deerinck T, Ellisman M, Johnson R, Karin M. The IKKbeta subunit of IkappaB kinase (IKK) is essential for nuclear factor kappaB activation and prevention of apoptosis. J Exp Med. 1999;189:1839–45.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Moreno JA, Izquierdo MC, Sanchez-Niño MD, Suárez-Alvarez B, Lopez-Larrea C, Jakubowski A, Blanco J, Ramirez R, Selgas R, Ruiz-Ortega M, Egido J, Ortiz A, Sanz AB. The inflammatory cytokines TWEAK and TNF{alpha} reduce renal klotho expression through NF{kappa}B. J Am Soc Nephrol. 2011;22:1315–25.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Neurath MF, Pettersson S, Meyer zum Büschenfelde KH, Strober W. Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappa B abrogates established experimental colitis in mice. Nat Med. 1996;2:998–1004.

    CrossRef  CAS  PubMed  Google Scholar 

  • Ortiz A, Husi H, Gonzalez-Lafuente L, Valiño-Rivas L, Fresno M, Sanz AB, Mullen W, Albalat A, Mezzano S, Vlahou T, Mischak H, Sanchez-Niño MD. Mitogen-activated protein kinase 14 promotes AKI. J Am Soc Nephrol. 2017;28(3):823–836.

    PubMed  PubMed Central  CrossRef  Google Scholar 

  • Pannicke U, Baumann B, Fuchs S, Henneke P, Rensing-Ehl A, Rizzi M, Janda A, Hese K, Schlesier M, Holzmann K, Borte S, Laux C, Rump EM, Rosenberg A, Zelinski T, Schrezenmeier H, Wirth T, Ehl S, Schroeder ML, Schwarz K. Deficiency of innate and acquired immunity caused by an IKBKB mutation. N Engl J Med. 2013;369(26):2504–14.

    CrossRef  CAS  PubMed  Google Scholar 

  • Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, Lee R, Tatevossian RG, Phoenix TN, Thiruvenkatam R, White E, Tang B, Orisme W, Gupta K, Rusch M, Chen X, Li Y, Nagahawhatte P, Hedlund E, Finkelstein D, Wu G, Shurtleff S, Easton J, Boggs K, Yergeau D, Vadodaria B, Mulder HL, Becksfort J, Gupta P, Huether R, Ma J, Song G, Gajjar A, Merchant T, Boop F, Smith AA, Ding L, Lu C, Ochoa K, Zhao D, Fulton RS, Fulton LL, Mardis ER, Wilson RK, Downing JR, Green DR, Zhang J, Ellison DW, Gilbertson RJ. C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. Nature. 2014;506(7489):451–5.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • 3Poveda J, Tabara LC, Fernandez-Fernandez B, Martin-Cleary C, Sanz AB, Selgas R, Ortiz A, Sanchez-Niño MD. TWEAK/Fn14 and Non-Canonical NF-kappaB Signaling in Kidney Disease. Front Immunol. 2013;4:447.

    Google Scholar 

  • Poveda J, Sanz AB, Rayego-Mateos S, Ruiz-Ortega M, Carrasco S, Ortiz A, Sanchez-Niño MD. NFκBiz protein downregulation in acute kidney injury: modulation of inflammation and survival in tubular cells. Biochim Biophys Acta. 2016;1862(4):635–46.

    CrossRef  CAS  PubMed  Google Scholar 

  • Quinton LJ, Blahna MT, Jones MR, Allen E, Ferrari JD, Hilliard KL, Zhang X, Sabharwal V, Algül H, Akira S, Schmid RM, Pelton SI, Spira A, Mizgerd JP. Hepatocyte-specific mutation of both NF-κB RelA and STAT3 abrogates the acute phase response in mice. J Clin Invest. 2012;122(5):1758–63.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Rackov G, Hernández-Jiménez E, Shokri R, Carmona-Rodríguez L, Mañes S, Álvarez-Mon M, López-Collazo E, Martínez-A C, Balomenos D. p21 mediates macrophage reprogramming through regulation of p50-p50 NF-κB and IFN-β. J Clin Invest. 2016;126(8):3089–103.

    PubMed  PubMed Central  CrossRef  Google Scholar 

  • Ruiz-Andres O, Suarez-Alvarez B, Sánchez-Ramos C, Monsalve M, Sanchez-Niño MD, Ruiz-Ortega M, Egido J, Ortiz A, Sanz AB. The inflammatory cytokine TWEAK decreases PGC-1α expression and mitochondrial function in acute kidney injury. Kidney Int. 2016;89(2):399–410.

    CrossRef  CAS  PubMed  Google Scholar 

  • Sanz AB, Sanchez-Niño MD, Izquierdo MC, Jakubowski A, Justo P, Blanco-Colio LM, Ruiz-Ortega M, Selgas R, Egido J, Ortiz A. TWEAK activates the non-canonical NFkappaB pathway in murine renal tubular cells: modulation of CCL21. PLoS One. 2010a;5:e8955.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Sanz AB, Sanchez-Niño MD, Ramos AM, Moreno JA, Santamaria B, Ruiz-Ortega M, Egido J, Ortiz A. NF-kappaB in renal inflammation. J Am Soc Nephrol. 2010b;21:1254–62.

    CrossRef  CAS  PubMed  Google Scholar 

  • Sen R, Baltimore D. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell. 1986;47:921–8.

    CrossRef  CAS  PubMed  Google Scholar 

  • Senftleben U, Cao Y, Xiao G, Greten FR, Krähn G, Bonizzi G, Chen Y, Hu Y, Fong A, Sun SC, Karin M. Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science. 2001;293:1495–9.

    CrossRef  CAS  PubMed  Google Scholar 

  • Sha WC, Liou HC, Tuomanen EI, Baltimore D. Targeted disruption of the p50 subunit of NF-kappa B leads to multifocal defects in immune responses. Cell. 1995;80:321–30.

    CrossRef  CAS  PubMed  Google Scholar 

  • Shinohara H, Behar M, Inoue K, Hiroshima M, Yasuda T, Nagashima T, Kimura S, Sanjo H, Maeda S, Yumoto N, Ki S, Akira S, Sako Y, Hoffmann A, Kurosaki T, Okada-Hatakeyama M. Positive feedback within a kinase signaling complex functions as a switch mechanism for NF-κB activation. Science. 2014;344(6185):760–4.

    CrossRef  CAS  PubMed  Google Scholar 

  • Song L, Liu L, Wu Z, Li Y, Ying Z, Lin C, Wu J, Hu B, Cheng SY, Li M, Li J. TGF-β induces miR-182 to sustain NF-κB activation in glioma subsets. J Clin Invest. 2012;122(10):3563–78.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Starokadomskyy P, Gluck N, Li H, Chen B, Wallis M, Maine GN, Mao X, Zaidi IW, Hein MY, McDonald FJ, Lenzner S, Zecha A, Ropers HH, Kuss AW, McGaughran J, Gecz J, Burstein E. CCDC22 deficiency in humans blunts activation of proinflammatory NF-κB signaling. J Clin Invest. 2013;123(5):2244–56.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Tilstra JS, Robinson AR, Wang J, Gregg SQ, Clauson CL, Reay DP, Nasto LA, St Croix CM, Usas A, Vo N, Huard J, Clemens PR, Stolz DB, Guttridge DC, Watkins SC, Garinis GA, Wang Y, Niedernhofer LJ, Robbins PD. NF-κB inhibition delays DNA damage-induced senescence and aging in mice. J Clin Invest. 2012;122(7):2601–12.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Van der Heiden K, Cuhlmann S, le Luong A, Zakkar M, Evans PC. Role of nuclear factor kappaB in cardiovascular health and disease. Clin Sci (Lond). 2010;118:593–605.

    CrossRef  CAS  Google Scholar 

  • Wietek C, Cleaver CS, Ludbrook V, Wilde J, White J, Bell DJ, Lee M, Dickson M, Ray KP, O’Neill LA. IkappaB kinase epsilon interacts with p52 and promotes transactivation via p65. J Biol Chem. 2006;281:34973–81.

    CrossRef  PubMed  Google Scholar 

  • Yamamoto Y, Gaynor RB. Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer. J Clin Invest. 2001;107:135–42.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Zhong Z, Umemura A, Sanchez-Lopez E, Liang S, Shalapour S, Wong J, He F, Boassa D, Perkins G, Ali SR, McGeough MD, Ellisman MH, Seki E, Gustafsson AB, Hoffman HM, Diaz-Meco MT, Moscat J, Karin M. NF-κB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria. Cell. 2016;164(5):89–910.

    CrossRef  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maria D. Sanchez-Niño .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2018 Springer International Publishing AG

About this entry

Verify currency and authenticity via CrossMark

Cite this entry

Valiño-Rivas, L., Gonzalez-Lafuente, L., Sanz, A.B., Poveda, J., Ortiz, A., Sanchez-Niño, M.D. (2018). NF-κB Family. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_220

Download citation