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Lecture 9a to post - Lecture 9 overview apoptosis what is...

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Lecture 9 overview apoptosis – what is it? how was it discovered – ced genes morphological features of apoptosis importance of programmed cell death in metazoans how do we detect and measure apoptosis what triggers apoptosis death signaling pathways – extrinsic death signaling pathways- intrinsic
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a physiological cell death program that controls normal cell numbers during development and disease. What is Apoptosis? (APE oh TOE sis)
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How was apoptosis discovered? 1972-proposed that normal cell deaths, as well as pathological ones, are suicides cells activate an intracellular death programme and kill themselves in a controlled way apoptosis is also referred to as: ‘programmed cell death’
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C. elegans as a model for apoptosis nematode worm Caenorhabditis elegans development of this organism has been very well studied organism has approximately 1000 cells when mature documented 131 cell deaths normally occur during development ….first evidence for genetic determinants of apoptosis and its control: if mutations in either of two genes (ced-3 and ced-4), then 131 cell deaths fail to occur
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protein encoded by ced-3 gene found to be very similar to a protein called: interleukin-1-converting enzyme (ICE) -an intracellular protein-cleaving enzyme (protease) that cuts out interleukin-1 from a larger precursor protein -death program depends on protein cleavage or proteolysis
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Components of the C. elegans death program ced-9 gene encodes a protein if inactivated, most of the cells in the developing worm die… if ced-4 and ced-3 are also inactivated in addition to ced-9, then apoptosis cannot occur and worm and all its cells live the ced-9 protein normally keeps the death programme suppressed in cells
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C. elegans as a model for apoptosis genetic studies in nematode first to show that caspases crucial for apoptosis ced-3 gene product is a caspase: essential for developmentally regulated apoptosis ced-4 gene product is structurally related to mammalian APAF-1: role in activation of caspase 9 in mammals ced-9 gene product structurally related to mammalian BCL-2: suppressor of apoptosis in mammals
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