Cell Apoptosis
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Transcript of Cell Apoptosis
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Lecture 5:
Apoptosis
Garland Science 2008
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II. Molecular mechanisms of Apoptosis?
I. What is apoptosis?
Required reading: pg. 1115-1128
Apoptosis
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Figure 18-1 Molecular Biology of the Cell( Garland Science 2008)
Two distinct forms of cell death
Apoptosis Cell necrosis
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Figure 18-2 Molecular Biology of the Cell( Garland Science 2008)
Programmed cell death eliminates unwantedcells during development
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Figure 18-3 Molecular Biology of the Cell( Garland Science 2008)
Apoptosis during frog metamorphosis
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Morphology of an apoptotic cell
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Figure 18-4a Molecular Biology of the Cell( Garland Science 2008)
Markers of apoptosis-Cleavage of nuclear DNA
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Figure 18-4b Molecular Biology of the Cell( Garland Science 2008)
Markers of apoptosis-TUNEL technique
TUNEL: TdT-mediated dUTP nick end labeling-TdT: terminal deoxynucleotidyl transferase
Label 3 cut ends of DNA fragments
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II. Molecular mechanisms of Apoptosis?
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Figure 18-5a Molecular Biology of the Cell( Garland Science 2008)
Apoptosis depends on an intracellularproteolytic cascadethat is mediated by
Caspases
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Figure 18-5b Molecular Biology of the Cell( Garland Science 2008)
Apoptosis depends on an intracellularproteolytic cascadethat is mediated by
Caspases
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Figure 18-6 Molecular Biology of the Cell( Garland Science 2008)
The extrinsic pathwayof apoptosis activatedthrough Fas death receptors
-DISC: Death-inducing signaling complex
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Figure 18-7 Molecular Biology of the Cell( Garland Science 2008)
The intrinsic pathwayof apoptosis dependson mitochondria
The release of cytochrome c frommitochondria during apoptosis
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Figure 18-8 Molecular Biology of the Cell( Garland Science 2008)
-Apaf1: apoptotic protease activating factor-1
-CARD: caspase recruitment domain
The intrinsic pathwayof apoptosis dependson mitochondria
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Figure 18-9 Molecular Biology of the Cell( Garland Science 2008)
Bcl2 proteins regulate the intrinsic pathway ofapoptosis
The three classes of Bcl2
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Figure 18-10 Molecular Biology of the Cell( Garland Science 2008)
The role of BH123pro-apoptotic Bcl2 proteinsin the release of mitochondrial intermembrane
proteins
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Figure 18-11a Molecular Biology of the Cell( Garland Science 2008)
How pro-apoptotic BH3-only and anti-apoptoticBcl2 proteins regulate the intrinsic pathway
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Figure 18-11b Molecular Biology of the Cell( Garland Science 2008)
How pro-apoptotic BH3-only and anti-apoptoticBcl2 proteins regulate the intrinsic pathway
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Figure 18-12a Molecular Biology of the Cell( Garland Science 2008)
IAPs inhibit caspases
-IAPs: inhibitors of apoptosis
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Figure 18-12b Molecular Biology of the Cell( Garland Science 2008)
The roles of IAPs and anti-IAPs in the control ofapoptosis
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Figure 18-13 Molecular Biology of the Cell( Garland Science 2008)
Extracellular survival factors inhibit apoptosis
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Figure 18-14 Molecular Biology of the Cell( Garland Science 2008)
Three ways that extracellular survival factorscan inhibit apoptosis
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Much of what is known about apoptosis comesfrom the study of C. elegans
Horvitz & Sulston
Wild type
Mutant for apoptosis
Fate of cells during C. elegans
development.
apoptoticcells
Adapted from Frank A. Laski
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Isolated apoptotic mutants in C. elegans andused epistatic analysis to order the genes in a
genetic pathway.
Adapted from Frank A. Laski
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1. Focal adhesion kinase (Fak)2. Lamins3. Cytoskeletal Proteins4. CAD - an endonuclease involved in DNA cleavage
(cleavage activates the enzyme)
5.
Enzymes involved in DNA repair6. Other caspases (activation of apoptotic cascade).
Targets of caspases
