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NF- κ B Signaling. Adam Johnson. What is NF- κ B?. Transcription Factor Dimer of Rel and NF- κ B proteins RelA RelB c- Rel p50 p52. Genes Transcribed. Kappa Light Chains (antibody) CFB (Complement Factor B) CD54 (ICAM-1) LBP (LPS binding) … Immune response!. Origin of NF- κ B.

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nf b signaling

NF-κB Signaling

Adam Johnson

what is nf b
What is NF-κB?
  • Transcription Factor
  • Dimer of Rel and NF-κB proteins
    • RelA
    • RelB
    • c-Rel
    • p50
    • p52
genes transcribed
Genes Transcribed
  • Kappa Light Chains (antibody)
  • CFB (Complement Factor B)
  • CD54 (ICAM-1)
  • LBP (LPS binding)
  • … Immune response!
origin of nf b
Origin of NF-κB
  • Originally thought to be “new”
  • Present in arthropods such as Drosophila
  • Not present in yeast or C. elegans
  • New research reveals NF-κB present in Capsaspora(possible precursor of multicellular animals)
  • Lots of untapped knowledge
origin of nf b1
Origin of NF-κB

Gilmore, T., & Wolenski, F. (2012)

pathway overview
Pathway Overview

Cell Signaling Technology, Inc.

slide7
IκB
  • In most cells, NF-κB sequestered by IκB
  • IκBs mask nuclear relocation signal
  • Phosphorylation of IκB by IKK leads to degradation in proteosome
  • NF-κB relocates to nucleus in absence of IκB
regulation of nf b
Regulation of NF-κB
  • NF-κB is self-regulated by negative feedback
  • NF-κB transcribes the genes for IκB
  • Composition of NF-κB dimer determines genes transcribed
canonical pathway
Canonical Pathway

Wikimedia Commons (2007)

non canonical pathway
Non-canonical Pathway
  • Primarily involved in lymphocytes
  • Instead of IκB, p52 precursor p100 part of the dimer
  • NIK (MAP3 kinase) activates IKK
  • IKK causes processing of p100 to p52
  • NF-κB relocates to nucleus
non canonical pathway1
Non-canonical Pathway

Gilmore (2006)

nik and cross talk
NIK and Cross-Talk
  • Small concentrations of NIK highly activate the non-canonical pathway
  • NIK activates canonical pathway at high concentrations
  • High levels of activation of both pathways lead to myeloma and lymphoma
nik regulation
NIK Regulation
  • Activated IKK targets NIK for degradation
  • NIK quickly bound by TRAF3
  • TRAF3 induces ubiquitination of NIK
  • To activate the non-canonical pathway, TRAF3 must be degraded
traf3 silencing
TRAF3 Silencing

Liao, et al (2004)

references
References
  • Cell Signaling Technology, Inc. (July 2009). NF-κB Signaling. Cell Signaling Technology. Retrieved March 19, 2013, from http://www.cellsignal.com/reference/pathway/NF_kappaB.html.
  • Gilmore, T. (2006). Introduction to NF-κB: players, pathways, perspectives. Oncogene, 25, 6680–6684.
  • Gilmore, T., & Wolenski, F. (2012). NF-κB: where did it come from and why?. Immunological Reviews, 246(1), 14-35.
  • Liao, G.; Zhang M.; HarhajE.; et al. (2004). Regulation of the NF-kappa B-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation. Journal of Biological Chemistry, 279(25), 26243-26250.
  • Sun, S. (2012). The noncanonical NF-κB pathway. Immunological Reviews, 246(1), 125-140.