NOTES - vivo Identification of active caspases in vivo...

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poptosis Apoptosis
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Proliferation Cell death Breast cancer cells T-cell attacking cancer cell www.sciencemuseum.org.uk
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Gewies, 2003
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Type I PCD Type II PCD Okada, 2004
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Lockshin, 2004
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WT L1 WAP-Bax L1 WAP-Bax L1 WAP-Bax L1 Apoptotic cells
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Translocase Scramblase Floppase
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TUNEL: terminal deoxynucleo- tidyltransferase-mediated dUTP nick Wap-Bax end labeling
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Apoptosome : Ced-9/Ced-4/Ced-3 ternary complex (Yang, Chan and altimore Science 1998) Baltimore, Science 1998). 3 genes cause cell death: egl-1 , ced-3, ced-4 ( C. elegans ce ll d eath genes) 1 gene promotes cell survival : (negative death regulator): ced-9
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ICE (Interleukin 1ß Converting Enzyme) Caspase 1 ( C ys catalytic Asp targeting prote ase) . 3% similarity with BCL 9% similarity 23% similarity with BCL-2 29% similarity Danial, 2004
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Hengartner, 2000
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ACXG Caspase activation Asp (D) Asp (D) QACXG a) Proteolytic activation b) Induced proximity ) poptosome formation c) Apoptosome formation Hengartner, 2000
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entification of active caspases
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Unformatted text preview: vivo Identification of active caspases in vivo Injection of caspase fluorogenic substrates into wild-type mouse 10x 40x R. Humphreys, unpublished Role of Diablo and IAP on Apoptosis Apaf-1 Caspase-9 cl-ytochrome c Bcl 2 Cytochrome c Caspase-3 Mitochondrion Ps Z-VAD IAPs mac/DIABLO second mitochondrial activator of caspases/ Smac/DIABLO direct IAP binding protein with low pI) Fesik, 2001 Cell membrane Procaspase-3 Caspase-3 Caspase-7 aspase ARP Mitochondrion Caspase-6 Lamin A Actin Gelsolin Fodrin CAD ICAD PARP DNA repair Cell shrinkage Membrane blebbing DNA degradation Cell membrane 15 kDa C-terminus More potent than WT BAD BAD Caspase-3 Caspase-7 aspase ARP Mitochondrion Caspase-6 Lamin A Actin Gelsolin Fodrin CAD ICAD PARP DNA repair Cell shrinkage Membrane blebbing DNA degradation Jurkat T-cells: rhodamine Macrophage: actin Savill, 2000...
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NOTES - vivo Identification of active caspases in vivo...

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