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Review article

Roles of NF-κB in health and disease: mechanisms and therapeutic potential

Ee Tsin Wong, Vinay Tergaonkar
Clinical Science Mar 01, 2009, 116 (6) 451-465; DOI: 10.1042/CS20080502
Ee Tsin Wong
Laboratory of NF-κB Signaling, Institute for Molecular and Cell Biology (A*STAR), 61, Proteos, 138673 Singapore
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Vinay Tergaonkar
Laboratory of NF-κB Signaling, Institute for Molecular and Cell Biology (A*STAR), 61, Proteos, 138673 Singapore
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Abstract

The NF-κB (nuclear factor κB) family of transcription factors are involved in a myriad of activities, including the regulation of immune responses, maturation of immune cells, development of secondary lymphoid organs and osteoclastogenesis. Fine tuning by positive and negative regulators keeps the NF-κB signalling pathway in check. Microbial products and genetic alterations in NF-κB and other signalling pathway components can lead to deregulation of NF-κB signalling in several human diseases, including cancers and chronic inflammatory disorders. NF-κB-pathway-specific therapies are being actively investigated, and these hold promises as interventions of NF-κB-related ailments.

  • cancer
  • inflammation
  • intracellular signalling
  • nuclear factor κB (NF-κB)
  • Rel

Abbreviations: ABC, activated B-cell-like; ALI, acute lung injury; API, apoptosis inhibitor; BAFF, B-cell-activating factor; BCR, B-cell receptor; CARD, caspase recruitment domain; CARMA, CARD-containing membrane-associated guanylate kinase protein; CBP, CREB (cAMP-response-element-binding protein)-binding protein; c-IAP, cellular inhibitor of apoptosis; CUEDC, CUE domain-containing protein; CYLD, cylindromatosis; DEN, diethylnitrosamine; DLBCL, diffuse large B-cell lymphoma; DUSP, dual-specificity phosphatase; ES, embryonic stem; GLUT, glucose transporter; HCC, hepatocellular carcinoma; HDAC, histone deacetylase; IBD, inflammatory bowel disease; IKK, IκB kinase; IL, interleukin; IL-1R, IL-1 receptor; ING, inhibitor of growth family member; IP, incontinentia pigmenti; IPD, invasive pneumococcal disease; IRAK, IL-1R-associated kinase; JNK, c-Jun N-terminal kinase; LPS, lipopolysaccharide; LT-β, lymphotoxin-β; MALT, mucosa-associated lymphatic tissue; CBM, CARMA1/Bcl-10/MALT1; MAPK, mitogen-activated protein kinase; MCP-1, monocyte chemoattractant protein-1; MEKK, MAPK/ERK (extracellular-signal-regulated kinase) kinase kinase; MM, multiple myeloma; MMP, matrix metalloproteinase; MSK, mitogen- and stress-activated kinase; MyD88, myeloid differentiation factor 88; NF-κB, nuclear factor κB; NEMO, NF-κB essential modulator; NBD, NEMO-binding domain; IκB, inhibitor of NF-κB; NIK, NF-κB-inducing kinase; oxPL, oxidized phospholipid; PKC, protein kinase C; PP1, protein phosphatase 1; PP2, protein phosphatase 2; RANK, receptor activator of NF-κB; RANKL, RANK ligand; RHD, REL homology domain; RIP, receptor-interacting protein; RNAi, RNA interference; RNS, reactive nitrogen species; ROS, reactive oxygen species; SAPK, stress-activated protein kinase; SHP, Src homology 2 domain-containing protein tyrosine phosphatase; siRNA, small interfering RNA; SNAP, soluble N-ethylmaleimide-sensitive fusion protein; STAT, signal transducer and activator of transcription; T2DM, Type 2 diabetes mellitus; TAK, TGF-β (transforming growth factor-β)-activated kinase; TCR, T-cell receptor; TIR, Toll/IL-1R; TLR, Toll-like receptor; TNF, tumour necrosis factor; TNFR, TNF receptor; TRAF, TNFR-associated factor; TRIF, TIR domain-containing adaptor protein inducing interferon-β; TrCP, transducin repeat-containing protein

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March 2009

Volume: 116 Issue: 6

Clinical Science: 116 (6)
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Roles of NF-κB in health and disease: mechanisms and therapeutic potential
Ee Tsin Wong, Vinay Tergaonkar
Clinical Science Mar 2009, 116 (6) 451-465; DOI: 10.1042/CS20080502
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Roles of NF-κB in health and disease: mechanisms and therapeutic potential
Ee Tsin Wong, Vinay Tergaonkar
Clinical Science Mar 2009, 116 (6) 451-465; DOI: 10.1042/CS20080502

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  • Article
    • Abstract
    • INTRODUCTION
    • ACTIVATION AND BIOLOGICAL FUNCTIONS OF THE CANONICAL PATHWAY
    • ACTIVATION AND BIOLOGICAL FUNCTIONS OF THE NON-CANONICAL PATHWAY
    • OTHER PROPOSED FUNCTIONS OF NF-κB AND IKK COMPLEX
    • POSITIVE REGULATORS OF NF-κB
    • CELLULAR INHIBITORS OF NF-κB
    • HUMAN DISEASES RESULTING FROM LOSS- OF-FUNCTION IN NF-κB SIGNALLING
    • HUMAN DISEASES RESULTING FROM GAIN- OF-FUNCTION IN NF-κB SIGNALLING
    • NF-κB SIGNALLING AS THERAPEUTIC TARGETS
    • FUTURE DIRECTIONS IN NF-κB-BASED THERAPEUTICS
    • FUNDING
    • Acknowledgments
    • References
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Keywords

cancer
inflammation
intracellular signalling
nuclear factor κB (NF-κB)
Rel

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