Post on 31-Mar-2015
NF-κB Signaling
Adam Johnson
What is NF-κB?Transcription FactorDimer of Rel and NF-κB proteins
RelA RelB c-Rel p50 p52
Genes TranscribedKappa Light Chains (antibody)CFB (Complement Factor B)CD54 (ICAM-1)LBP (LPS binding)… Immune response!
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-κB
Gilmore, T., & Wolenski, F. (2012)
Pathway Overview
Cell Signaling Technology, Inc.
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-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
Wikimedia Commons (2007)
Non-canonical PathwayPrimarily 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 Pathway
Gilmore (2006)
NIK and Cross-TalkSmall 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 RegulationActivated IKK targets NIK for degradation
NIK quickly bound by TRAF3TRAF3 induces ubiquitination of NIK
To activate the non-canonical pathway, TRAF3 must be degraded
TRAF3 Silencing
Liao, et al (2004)
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.; Harhaj E.; 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.