1 / 15

NF- κ B Signaling

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.

audra-velez
Download Presentation

NF- κ B Signaling

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. NF-κB Signaling Adam Johnson

  2. What is NF-κB? • Transcription Factor • Dimer of Rel and NF-κB proteins • RelA • RelB • c-Rel • p50 • p52

  3. Genes Transcribed • Kappa Light Chains (antibody) • CFB (Complement Factor B) • CD54 (ICAM-1) • LBP (LPS binding) • … Immune response!

  4. 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

  5. Origin of NF-κB Gilmore, T., & Wolenski, F. (2012)

  6. Pathway Overview Cell Signaling Technology, Inc.

  7. 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

  8. 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

  9. Canonical Pathway Wikimedia Commons (2007)

  10. 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

  11. Non-canonical Pathway Gilmore (2006)

  12. 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

  13. 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

  14. TRAF3 Silencing Liao, et al (2004)

  15. 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.

More Related