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.

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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. 

 

**TNF-α Activation of the TNF Receptor: An Overview**

TNF-α activation of the TNF receptor stimulates two divergent signaling pathways: a protease cascade, leading to cell death, and a phosphorylation cascade, leading to cell survival. These pathways diverge at the level of the TRADD protein, which binds TNF receptor-associated factor 2 (TRAF2).

**Apoptotic Pathway:**
1. **TNF Receptor-Mediated Assembly:** Activation leads to the assembly of DD (death domain) and DED (death effector domain) protein complexes, involving TRADD and FADD.
2. **Autocleavage of Procaspase 8:** This results in the formation of caspase 8 (CASP8), promoting a proteolytic cascade.
3. **CASP8 Activation:** Leads to the cleavage and activation of caspase 3 (CASP3), known as the "executioner" protease.
4. **Cell Death Execution:** CASP3 cleaves various cellular proteins, leading to cell death.

**Cell Survival Pathway:**
1. **NIK/RIP-Mediated Phosphorylation:** TRAF2 promotes the activation of receptor-interacting protein (RIP) kinase, phosphorylating IKK.
2. **IKK Activation:** Leads to the phosphorylation and degradation of IκBα, allowing NFκB activation.
3. **NFκB Translocation:** The active NFκB (p50/p65) translocates to the nucleus.
4. **Gene Expression Modulation:** NFκB induces the expression of anti-apoptotic genes that inhibit caspase 8 and caspase 3 activation, promoting cell survival.

**Graphical Elements:**
- The diagram shows TNFα binding to TNF receptors on the plasma membrane, initiating the described pathways.
- The apoptotic pathway is illustrated as a cascade of interactions culminating in cell death.
- The cell survival pathway is visualized through a series of phosphorylation events leading to gene expression changes inside the nucleus.

This dual pathway system exemplifies the complexity of cellular responses to external signals, balancing between survival and programmed cell death.
Transcribed Image Text:**TNF-α Activation of the TNF Receptor: An Overview** TNF-α activation of the TNF receptor stimulates two divergent signaling pathways: a protease cascade, leading to cell death, and a phosphorylation cascade, leading to cell survival. These pathways diverge at the level of the TRADD protein, which binds TNF receptor-associated factor 2 (TRAF2). **Apoptotic Pathway:** 1. **TNF Receptor-Mediated Assembly:** Activation leads to the assembly of DD (death domain) and DED (death effector domain) protein complexes, involving TRADD and FADD. 2. **Autocleavage of Procaspase 8:** This results in the formation of caspase 8 (CASP8), promoting a proteolytic cascade. 3. **CASP8 Activation:** Leads to the cleavage and activation of caspase 3 (CASP3), known as the "executioner" protease. 4. **Cell Death Execution:** CASP3 cleaves various cellular proteins, leading to cell death. **Cell Survival Pathway:** 1. **NIK/RIP-Mediated Phosphorylation:** TRAF2 promotes the activation of receptor-interacting protein (RIP) kinase, phosphorylating IKK. 2. **IKK Activation:** Leads to the phosphorylation and degradation of IκBα, allowing NFκB activation. 3. **NFκB Translocation:** The active NFκB (p50/p65) translocates to the nucleus. 4. **Gene Expression Modulation:** NFκB induces the expression of anti-apoptotic genes that inhibit caspase 8 and caspase 3 activation, promoting cell survival. **Graphical Elements:** - The diagram shows TNFα binding to TNF receptors on the plasma membrane, initiating the described pathways. - The apoptotic pathway is illustrated as a cascade of interactions culminating in cell death. - The cell survival pathway is visualized through a series of phosphorylation events leading to gene expression changes inside the nucleus. This dual pathway system exemplifies the complexity of cellular responses to external signals, balancing between survival and programmed cell death.
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