Sp10 BIO 314 Chap 9 part 2

Sp10 BIO 314 Chap 9 part 2 - Apoptosis Programmed cell...

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1/5/11 Apoptosis Programmed cell death (as opposed to accidental, ie by injury, etc.) Occurs normally during development, morphogenesis, etc. It is a discrete, genetically controlled, evolutionarily conserved, predictable, reproducible program of cell dissolution. It eliminates damaged and deranged cells, and is therefore tumor suppressive; potential
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1/5/11 Figure 913 The Biology of Cancer (© Garland Science 2007) Stress kinases PO4 p53 (and mdm 2). These PO4’s disrupt the p53:mdm2 interaction and therefore stabilize the p53 protein. survival signals promote mdm2 expression survival signals promote mdm2 mediated p53 degradation stress signals promote p53 stabilization
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1/5/11 Figure 9.17 The Biology of Cancer (© Garland Science 2007) Tumor cells have elevated levels of mutant p53 protein. Mutant p53 is unable to transactivate mdm2, so p53 is not degraded.
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1/5/11 In response to stress, p53 becomes PO4’d. This modification interfere’s with p53:mdm2 complexing, so mdm2 can no longer degrade p53. p53 levels accumulate rapidly, and p53 becomes an active transcription factor. p53 target genes promote growth arrest, DNA repair and apoptosis
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1/5/11 Table 9.2 The Biology of Cancer (© Garland Science 2007)
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1/5/11 We already know about growth arrest… p53 targets are the inhibitors of cyclin:CDK’s that promote cell cycle progression. DNA repair: chapter 12 (genome integrity) What about apoptosis? How exactly does the cell dissolve itself? By activating a family of enzymes (nucleases, proteases, etc) that systematically “digest” the cell. (At least its not another kinase cascade…. .)
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1/5/11 Apoptosis is about more than cancer: Apoptosis occurs during normal embryonic development. Apoptosis is responsible for death of anoxic tissue following ie stroke, heart attack. Apoptosis may also play a role in neuro-degenerative diseases such
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1/5/11 Figure 9.19 The Biology of Cancer (© Garland Science 2007) An example of developmental apoptosis (“sculpting”)
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An example of apoptosis following anoxia (ischemia). Green indicates activation of one of the proteolytic enzymes (caspase 3) Cell Signaling Technologies
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1/5/11 Figure 9.21 The Biology of Cancer (© Garland Science 2007) Anoikis (homelessness). Epithelial cells (MECs) that have lost their attachment to the ECM undergo apoptosis. (work of J.Brugge) Green= marker for apoptosis Blue = nuclei Red = integrins (PM proteins that serve as receptors for ECM ligands)
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1/5/11 Figure 9.18a The Biology of Cancer (© Garland Science 2007) This is the surface of an apoptotic cell, the membrane “blebs” are characteristic of apoptosis
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1/5/11 Figure 9.18b The Biology of Cancer (© Garland Science 2007) These are nuclei: the ones on the left are healthy size and shape, and homogeneously stained.
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Sp10 BIO 314 Chap 9 part 2 - Apoptosis Programmed cell...

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