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Tnf alpha presentation
Tnf alpha presentation
Tnf alpha presentation
Tnf alpha presentation
Tnf alpha presentation
Tnf alpha presentation
Tnf alpha presentation
Tnf alpha presentation
Tnf alpha presentation
Tnf alpha presentation
Tnf alpha presentation
Tnf alpha presentation
Tnf alpha presentation
Tnf alpha presentation
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Tnf alpha presentation

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  • 1. Tumor Necrosis Factor Implication Of Apoptosis and Cell Growth Arun kumar Pradhan ONA Odisha NET Academy-09337727724
  • 2. TNF α •Also called cachectin •Produced by macrophages and Mast cells •TNF alpha is a inflammatory cytokine •Target tissue: tumour cells and Inflammatory cells •Responsible for extensive weight loss (cachexia) associated with chronic inflammation. TNF β •Also called lymphotoxin •produced by TH1 and Tc cells •Target tissue: tumour cells and macrophage and neutrophils •Has cytotoxic activity • Enhances the phagocytic activity. Apoptosis:- • Apoptosis from Greek, meaning “falling off” (also called programmed cell death) • Complex program of self-destruction,triggered by a variety of stimuli and involving the activation of caspase enzymes, that results in quick fragmentation and phagocytosis of a cell Odisha NET Academy-09337727724
  • 3. D D I S C Odisha NET Academy-09337727724
  • 4. DEATH signals TNF- alpha / CD95 ligand / Fas ligand Death receptors, e.g. CD95 Death domains Odisha NET Academy-09337727724
  • 5. Binding to the receptor induces receptors to cluster and trimerize After binding to ligand, receptors form trimers Death domains TNF/Fas ligand trimer Odisha NET Academy-09337727724
  • 6. FADD (Fas associated death domain protein) is recruited via its death domain DED (death effector domain) of FADD recruits pro-caspase 8 via its DED FADD-CASP8 complex brings multiple pro-caspase 8 molecules in close proximity (‘induced proximity’ aggregation results in their cross-activation). Activated caspase-8 (a heterotetramer) is released from DISC into the cytoplasm DISC comple x Odisha NET Academy-09337727724
  • 7. caspase-8 cleaves pro-apoptotic BID protein. BID interacts with the pro-apoptotic BCL2 relatives BAX and BAK This amplifies apoptosis induction through the cell-extrinsic pathway Odisha NET Academy-09337727724
  • 8. Apoptosome: “wheel of death” The Mitochondrial Apoptotic pathway Bax,Bak Bcl-2,Bcl XL Caspase-8 signal or Pro apoptotic signal dominants on Anti apoptotic signal Inh ibits Odisha NET Academy-09337727724
  • 9. TNF-alpha caN sigNal To NF-kB TraNscripTioN FacTors *NF-kB factors are mostly anti-apoptotic Activate pro-survival Bcl-XL,Bcl-2 IAPs Activate pro-apoptotic FAS, FAS Ligand P53 inflammatory cytokines, chemokines, immunoreceptors, and cell adhesion molecules Tissue specific decision One of the `central mediators of the immune response NF-kB Odisha NET Academy-09337727724
  • 10. TNF-alpha can signal to NF-kappaB transcription factors. Binding of TNF-alpha to TNFR TRADD recruited IKK kinase recruited IKK phosphorylate IkB IkB degraded P50/p65 (NF-kappaB) Free to act as TF Odisha NET Academy-09337727724
  • 11. TNF-alpha can signal to NF-kappaB transcription factors. In the cytoplasm, NF-kB is inhibited by IkB (inhibiitor of NF-kappa B) Upstream activating signal (e.g., binding of TNF to its receptor) may cause phosphorylation of IkB by IKK (IkB kinase). Cell survival & GrowthOdisha NET Academy-09337727724
  • 12. What is the molecular basis of the Paradox? Cellular Context NFκB: Life Caspases: death IL-1 TNFα Conclusion: Odisha NET Academy-09337727724
  • 13. ?Odisha NET Academy-09337727724
  • 14. Thank ouOdisha NET Academy-09337727724

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