NF- κ B Signaling

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NF-κB Signaling Adam Johnson

description

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

Transcript of NF- κ B Signaling

Page 1: NF- κ B Signaling

NF-κB Signaling

Adam Johnson

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What is NF-κB?Transcription FactorDimer of Rel and NF-κB proteins

RelA RelB c-Rel p50 p52

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

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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

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Origin of NF-κB

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

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Pathway Overview

Cell Signaling Technology, Inc.

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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

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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

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Canonical Pathway

Wikimedia Commons (2007)

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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

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Non-canonical Pathway

Gilmore (2006)

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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

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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

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TRAF3 Silencing

Liao, et al (2004)

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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.