Explain the general steps in the pathway (use figure 8.53). Make sure to include an explanation of the proteolytic and phosphorylation cascades. What advantage is there in having a cascade part of these pathways? What purpose does it serve?Please when explaining the general steps, please explain them as thoroughly and detailed as you can possibly be. Apoptotic pathwayTNF receptor-mediatedassembly of DD and DEDprotein complexesProcaspase 82 Autocleavage ofprocaspase 83 CASP8 cleavage ofprocaspase 3Procaspase 3CASP3 cleavage ofcellular proteinsTNFreceptorsDeathdomainsFADDCASP8CASP3TNF-αCelldeathTRADDTRAF2IKKInactiveNIKATPRIPCellsurvivalADPCell survival pathway1 NIK/RIP-mediatedphosphorylation of IKKIKKATPPADPp50IkBap65Plasmamembrane.IKK phosphorylationof IkBa results inactivation of p50/p65ActiveNFkB45Increased expressionof anti-apoptotic genesthat inhibit CASP8 andCASP3 activationFigure 8.53 TNF-a activation of the TNF receptorstimulates both a protease cascade, leading to cell death,and a phosphorylation cascade, resulting in cell survivalThe two signaling pathways diverge at the level of theTRADD protein, which contains both a DD and an N-terminal domain that binds TNF receptor-associatedfactor 2 (TRAF2). In the apoptosis pathway, TNFreceptor activation leads to assembly of a TRADD-Active p50/p65heterodimericNFKB translocatesto the nucleusNuclearmembrane.FADD complex that results in autocleavage of procaspas8 through its interaction with the death effector domain(DED) of FADD. Once caspase 8 (CASP8) is activated,proteolytic cascade is initiated by the cleavage andactivation of caspase 3 (CASP3), the "executioner”protease. TNF receptor signaling can also induce a cellsurvival pathway through an adaptor complex consistingof TRADD, TRAF2, and receptor interacting protein(RIP) kinase, which leads to the phosphorylation andactivation of IkBa kinase (IKK). Phosphorylation of IKBby IKK targets IKBa for degradation, which leads toactivation of the transcription factor NFKB. Once theheterodimeric NFkB (p50/p65) transcription factor isactivated, it enters the nucleus and induces the expressioof anti-apoptotic genes that inhibit caspase 8 and caspas3 activation.

TNF is a member of the soluble cytokine family. By generating soluble receptors that engage…

Explain the general steps in the pathway (use figure 8.53). Make sure to include an explanation of the proteolytic and phosphorylation cascades. What advantage is there in having a cascade part of these pathways? What purpose does it serve? Please when explaining the general steps, please explain them as thoroughly and detailed as you can possibly be.

Explain the general steps in the pathway (use figure 8.53). Make sure to include an explanation of the proteolytic and phosphorylation cascades. What advantage is there in having a cascade part of these pathways? What purpose does it serve? Please when explaining the general steps, please explain them as thoroughly and detailed as you can possibly be.

Principles Of Pharmacology Med Assist

6th Edition

ISBN:9781337512442

Author:RICE

Publisher:RICE

Chapter27: Medications That Affect The Nervous System

Section: Chapter Questions

Problem 25RQ

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