NF- κ B Signaling

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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. - PowerPoint PPT Presentation

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NF-B SignalingAdam JohnsonWhat is NF-B?Transcription FactorDimer of Rel and NF-B proteinsRelARelBc-Relp50p52

Genes TranscribedKappa Light Chains (antibody)CFB (Complement Factor B)CD54 (ICAM-1)LBP (LPS binding) Immune response!

Origin of NF-B Originally thought to be newPresent in arthropods such as DrosophilaNot present in yeast or C. elegansNew research reveals NF- B present in Capsaspora (possible precursor of multicellular animals)Lots of untapped knowledge

Origin of NF-B

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

Cell Signaling Technology, Inc.IBIn most cells, NF-B sequestered by IBIBs mask nuclear relocation signalPhosphorylation of IB by IKK leads to degradation in proteosomeNF-B relocates to nucleus in absence of IB

Regulation of NF-B NF-B is self-regulated by negative feedbackNF-B transcribes the genes for IBComposition of NF-B dimer determines genes transcribed

Canonical Pathway

Wikimedia Commons (2007)Non-canonical PathwayPrimarily involved in lymphocytesInstead of IB, p52 precursor p100 part of the dimerNIK (MAP3 kinase) activates IKKIKK causes processing of p100 to p52NF-B relocates to nucleus

Non-canonical Pathway

Gilmore (2006)NIK and Cross-TalkSmall concentrations of NIK highly activate the non-canonical pathwayNIK activates canonical pathway at high concentrationsHigh levels of activation of both pathways lead to myeloma and lymphomaNIK RegulationActivated IKK targets NIK for degradationNIK quickly bound by TRAF3TRAF3 induces ubiquitination of NIKTo activate the non-canonical pathway, TRAF3 must be degradedTRAF3 Silencing

Liao, et al (2004)ReferencesCell Signaling Technology, Inc. (July 2009). NF-B Signaling. Cell Signaling Technology. Retrieved March 19, 2013, from http://www.cellsignal.com/reference/pathway/NF_kappaB.html.Gilmore, T. (2006). Introduction to NF-B: players, pathways, perspectives. Oncogene, 25, 66806684.Gilmore, T., & Wolenski, F. (2012). NF-B: 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-B pathway. Immunological Reviews, 246(1), 125-140.