Apoptosis Pathways
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Questions and Answers

What is the primary function of Fas ligand in the immune system and cancer progression?

  • Promoting cell proliferation and differentiation
  • Regulating gene expression and transcription
  • Activating the inflammatory response
  • Inducing apoptosis through receptor binding (correct)

    • What is the main difference between the extrinsic and intrinsic apoptotic pathways?

  • One is exclusive to vertebrates, while the other is not
  • One is mediated by caspases, while the other is not
  • One involves the release of cytochrome c, while the other does not
  • One is activated by death receptors, while the other is not (correct)

    • What is the role of BID in death receptor-mediated apoptosis?

  • Regulating gene expression and transcription
  • Inhibiting the release of apoptogenic proteins
  • Facilitating the release of cytochrome c from the mitochondria (correct)
  • Activating the inflammatory response

    • What is the final outcome of both the extrinsic and intrinsic apoptotic pathways?

    <p>Activation of caspases leading to cell death</p> Signup and view all the answers

    What is the primary function of APAF-1 in the intrinsic apoptotic pathway?

    <p>Activating caspases leading to cell death</p> Signup and view all the answers

    What is released from mitochondria, contributing to apoptosis even in the absence of caspase activation?

    <p>AIF and EndoG</p> Signup and view all the answers

    What is the function of the WD40 motif in APAF-1?

    <p>It negatively regulates APAF-1 activity</p> Signup and view all the answers

    What triggers the formation of the active apoptosome?

    <p>Binding of dATP/ATP to APAF-1</p> Signup and view all the answers

    What is the function of the apoptosome?

    <p>Recruitment of procaspase-9 and activation of downstream caspases</p> Signup and view all the answers

    What is the outcome of the activation of caspase-3 and caspase-7?

    <p>Cell death and apoptosis</p> Signup and view all the answers

    Study Notes

    Apoptosis Pathways

    • There are two pathways that trigger apoptosis: the extrinsic and intrinsic (mitochondrial) apoptotic pathways
    • The extrinsic pathway, also known as the "death receptor pathway", is activated by the engagement of death receptors on the cell surface
    • The intrinsic pathway involves the release of cytochrome c (and other proteins) from the mitochondria

    Intrinsic Pathway

    • The intrinsic pathway is also known as the mitochondrial pathway
    • The majority of apoptosis in vertebrates proceeds through the mitochondrial pathway
    • The release of cytochrome c from the mitochondria is a crucial step in the intrinsic pathway

    Fas Ligand and Fas Receptor

    • Fas ligand (FasL or CD95L or CD178) is a type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family
    • Fas ligand/receptor interactions play an important role in the regulation of the immune system and the progression of cancer

    BID and MOMP

    • BID is an abundant pro-apoptotic protein of the Bcl-2 family that is crucial for death receptor-mediated apoptosis in many cell systems
    • BID action involves the mitochondrial re-location of its truncated form, tBID, to facilitate the release of apoptogenic proteins like cytochrome c
    • MOMP (Mitochondrial Outer Membrane Permeabilization) releases two inhibitors of IAPs, DIABLO/Smac and Omi/HtrA2
    • MOMP also releases other important proteins, including AIF (apoptosis-induction factor) and endonuclease G (EndoG)

    Apoptosome

    • The apoptosome is a complex that activates procaspase-9
    • The apoptosome is formed when cytochrome c associates with APAF-1
    • APAF-1 is a cytosolic protein that contains a caspase recruitment domain (CARD), a nucleotide binding domain (NBD), and a long C-terminal extension containing 13 repeats of the WD40 motif

    APAF-1 and Formation of the Apoptosome

    • APAF-1 is in an inactive state until cytochrome c engages the WD40 repeats
    • Association with cytochrome c triggers a conformational change in APAF-1, allowing it to form the active apoptosome
    • The apoptosome is a wheel-like structure that recruits procaspase-9 into its central hub through CARD-CARD domain interaction between procaspase-9 and APAF-1 molecules

    Activation of Caspases

    • The formation of the apoptosome triggers the activation of procaspase-9
    • Active procaspase-9 can then activate downstream executioner caspases, such as caspase-3 and caspase-7
    • These caspases ultimately lead to cell death

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    Description

    This quiz covers the two main pathways that trigger apoptosis, including the extrinsic and intrinsic pathways, and their mechanisms in inducing cell death.

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