Naturally Programmed Cell Death, Apoptosis, and Cancer

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Naturally Programmed Cell Death, Apoptosis, and
Cancer
Folder Title Apoptose

• or ...

December 1, 2004
TtlApop
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What happened to your webbed feet? You guys are
dethpicable.
DaffyDuc
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God and Michelangelo

• Creation by Subtraction

Evolution Selective Reproduction
Selective Death
Subtract
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Selective Cell Death in Normal Development and
Normal Organismic Functioning

• Developmental Remodelling
• Tadpole to Frog
• Human Fetal Remodelling
• Immunological Self-Tolerance
• Normal Physiology
• Post-Lactation Breast Involution
• Menstruation
• Normal Immune T-Cell Killing

NormApop
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(No Transcript)
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Necrosis vs Apoptosis

• Necrosis
• Clumped Chromatin
• Swelling of Organelles
• Cell Distension
• Membrane Disruption
• Inflammation

Apoptosis Condensed Nuclear Fragments Shrunken
Cytoplasm Membrane Blebs (Apoptotic
Bodies) Phagocytosis without Inflammation
KillDie
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Apoptotic Cell. Ruddon, 3rd Ed. Fig. 10-7
ApoCell
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Membrane Blebs on a Cell
Undergoing Apoptosis from
Scientific American, December, 1996
ApoBlebs
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DNA Lysis into "DNA Ladder". DNA from
Apoptotic Cell. From Ruddon, 3rd Ed., Figure 10-8
ApoDNA
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Genetic Control of "Genetically Programmed Cell
Death"

• Cellular Location of Protein Product
• Mitochondrial Membrane
• Nuclear Envelope
• Endoplasmic Reticulum
• Nucleus
• Nucleus
• Cell Membrane

Apoptosis Gene
Effect on Apoptosis Blocks Stimulates Wild-ty
pe Stimulates Mutant Blocks Stimulates
bcl-2
myc
p53 p53
APO-1/ FAS
ApoGenes
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Exogenous Genetic Suppressors of Apoptosis

• Adenovirus E1b Oncoprotein
• Ras
• v-abl
• compox crm a gene product

ExoApop1
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Exogenous Inducers of Apoptosis

• Cytotoxic T-Lymphocyte Attack on Target Cells
• Loss of Growth Factors
• Loss of Responses from Neighboring Cells
• DNA-Directed Anti-Neoplastic Agents

ExoApop2
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More Exogenous Inducers of Apoptosis(from
Ruddon, 3rd Ed., p. 397)

• Differentiation Signals
• Removal of Growth Factors or Required Hormones
• Exposure to Transforming Growth Factor B (TGF-B)
• Tumor Necrosis Factor (TNF)
• Glucocorticoids (Immune-modulating
  Corticosteroids)
• DNA-damaging Antineoplastic Agents
• Environmental Toxins
• Agents Stimulating Ca Influx (Calcium
  Ionophores)
• Cytoskeletal-directed Microtubule Disruptors
• Microfilament-directed Cytochalasin B Inhibits
  formation of Apoptotic Bodies, but not apoptosis
  itself

ExoApop3
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Normal T-Cell Activation by Antigen-Presenting
Cells. (from Sci. Am., Dec, 1996)
TCellAct
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Activated T-Cell Down-regulation via FAS
Cell-Surface Protein and Ligand Binding to FAS.
(from Sci. Am., Dec., 1996)
TCelDown