Transcript Naturally Programmed Cell Death, Apoptosis, and Cancer

Naturally Programmed
Cell Death,
Apoptosis, and Cancer
Folder Title: Apoptose
or ...
December 1, 2004
TtlApop
What happened to
your webbed feet?
You guys are
dethpicable.
DaffyDuc
God and Michelangelo
Creation by Subtraction
Evolution:
Selective Reproduction
Selective Death
Subtract
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
Necrosis vs Apoptosis
Necrosis
Apoptosis
Clumped Chromatin
Swelling of
Organelles
Cell Distension
Membrane
Disruption
Inflammation
Condensed Nuclear Fragments
Shrunken Cytoplasm
Membrane Blebs (Apoptotic
Bodies)
Phagocytosis without
Inflammation
Kill&Die
Apoptotic Cell. Ruddon, 3rd Ed.
Fig. 10-7
ApoCell
Membrane Blebs
on a Cell
Undergoing
Apoptosis
from Scientific American,
December, 1996
ApoBlebs
DNA Lysis into
"DNA Ladder".
DNA from Apoptotic
Cell.
From Ruddon, 3rd Ed.,
Figure 10-8
ApoDNA
Genetic Control of "Genetically
Programmed Cell Death"
Apoptosis Cellular Location of
Gene
Protein Product
bcl-2
Effect on Apoptosis
Mitochondrial Membrane Blocks
myc
Nuclear Envelope
Endoplasmic Reticulum
Stimulates
p53
Nucleus
Nucleus
Wild-type Stimulates
Mutant Blocks
p53*
APO-1/ Cell Membrane
FAS
Stimulates
ApoGenes
Exogenous Genetic Suppressors of
Apoptosis
Adenovirus E1b Oncoprotein
Ras
v-abl
compox crm a gene product
ExoApop1
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
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
Normal T-Cell Activation by
Antigen-Presenting Cells. (from Sci. Am., Dec, 1996)
TCellAct
Activated T-Cell Down-regulation via FAS Cell-Surface
Protein and Ligand Binding to FAS. (from Sci. Am., Dec., 1996)
TCelDown