NF- κ B Signaling

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.

NF- κ B Signaling

Documents

Transcript of NF- κ B Signaling

Supplemental Information A Cytoplasmic ATM-TRAF6 · PDF fileSupplemental Information A Cytoplasmic ATM-TRAF6-cIAP1 Module Links Nuclear DNA Damage Signaling to Ubiquitin-Mediated NF-

Progesterone Administration Modulates TLRs/NF-κB Signaling ... · Progesterone Administration Modulates TLRs/NF-κB Signaling Pathway in Rat Brain after Cortical Contusion Gang Chen,1

BCR-signaling synergizes with TLR-signaling to …BCR-signaling synergizes with TLR-signaling to induce AID and immunoglobulin class-switching through the non-canonical NF-κB pathway

Supplementary Figure.1 NF- κ B p65 / β- actin protein ** ID8HM-1 1 2 3 ** * * * β-actin ID8 HM-1 +CPA(0.7uM)non-treat+CPA(7uM)+CPA(70uM) NF-κB p65 β-actin.

CX3CL1 promotes MMP-3 production via the CX3CR1, c-Raf ...€¦ · signaling pathway. Luciferase assays were used to study NF-κB promoter activity. Results: We investigated the signaling

Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

Curcumin a Potential Cancer Chemopreventive Agent through Suppressing NF-κB Signaling

Signaling for apoptosis induced by topoisomerase poisons · Signaling for apoptosis induced by topoisomerase poisons 4 topoisomerase poison induced apoptotic cell death. NF-κB is

Structural studies of NF-κB signaling - Harvard Universitywulab.tch.harvard.edu/PDF/StructuralStudiesofNF-kBSignaling.pdf · IκBs bind NF-κB dimer with at least one p65 or c-Rel

Inhibition of the NF-κB Signaling Pathway by a Novel ......Molecules 2015, 20 867 Figure 3. BAT3 inhibits NF-κB-driven reporter gene expression. L929sA cells stably transfected with

Simultaneous Analysis of Wnt and NF-κB Signaling Pathways ... · Simultaneous analysis of Wnt and NF-κB signaling pathways in doxorubicin sensitive and methotrexate resistant PLC/PRF/5

Islet α-cell Inflammation Induced By NF-κB inducing …thno.org/v08p5960.pdfResults: The LTβR/noncanonical NF-κB signaling pathway is present in islet α cells. Overexpression

Effect of canonical NF-κB signaling pathway on the ... · NF-κB signaling pathway and many other signaling pathways such as Notch signaling, TGF-β/SMAD sig-naling, p53 signaling,

TLR4/NF-κB signaling pathway-mediated and oxLDL-induced up ... · which protein expressions of LOX-1, MCP-1, and VCAM-1, and the nuclear translocation of NF-kB (P50) were detected

IL-1β Inhibits BKV Replication in Human Renal Proximal Tubular Cellsckbjimmy.github.io/docs/weng2009bkv.pdf · 2020. 10. 20. · • TAK1-NF-κB signaling pathway is indispensable

INVESTIGATION OF EPITHELIAL CANONICAL AND NON-CANONICAL …etd.library.vanderbilt.edu/available/etd-02092016... · INVESTIGATION OF EPITHELIAL CANONICAL AND NON-CANONICAL NF-κB SIGNALING

MiR-146a regulates the development of ulcerative colitis ... · TLR4/MyD88/NF-κB signaling pathway. Key Words: MiR-146a, Ulcerative colitis, TLR4, MyD88, NF-κB. Introduction Ulcerative

Influences of miR-155/NF-κB signaling pathway on ...MiR-155/NF-κB signaling pathway, ARDS in neona-tal pigs, Inflammatory factors, influences. Introduction Acute respiratory distress

NF- κ B-Inhibiting Naphthopyrones from the Fijian Echinoderm Comanthus parvicirrus

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.

Supplementary Figure.1 NF- κ B p65 / β- actin protein ID8HM-1 1 2 3 * * * β-actin ID8 HM-1 +CPA(0.7uM)non-treat+CPA(7uM)+CPA(70uM) NF-κB p65 β-actin.