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lecture18 - Combinatorial Control IFN enhancer Drosophila...

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1801 Combinatorial Control IFN β enhancer Drosophila development Temporal Control p53 NF κ B
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1802 p53-mdm2 oscillations Are these happening in normal cells? If so, are they functionally important?
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1803 NF κ B is activated by many stimuli IKK NF- κ B I κ B NF- κ B NF- κ B ε β α nucleus cytoplasm signaling module feedback mechanisms generate interesting temporal control of NF κ B Is temporal control important? cytokines e.g. TNF pathogens e.g. LPS
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1804 RFP-NF κ B (a red fluorescent proteins fused to NFkB)
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1805 wt IKK NF- κ B IKK KA EMSA 0 15 30 45 60 75 90 105120 0 10 15 30 45 60 90 120 TNF LPS Stimulus-specific temporal control of IKK and NF- κ B TNF LPS early and transient delayed and sustained TNF LPS A: 79 B: 36 C: 22 D: 60 E: 111 F: 16 G: 43 H: 51 I: 44 J: 134 K: 73 different gene expression programs
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1806 NF- κ B IKK TNF LPS NF κ B temp mutant module IKK TNF LPS NF- κ B ?? Is temporal control of NF- κ B important for stimulus-specific gene expression ?
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1807 α β ε α β ε α β ε AAAAAAA nucleus cytoplasm IKK 7,9,11 54,55,56 66,67,68 α β ε 60,61,62 69 71 72 70 73 63,64,65 44 41,42,43 34,35,36 37 51,52,53 22,24,26 46,48,50 57,58,59 A α β ε α β ε IKK IKK α β ε 45,47,49 23,25,27 8,10,12 13,14,15 28,29,30 2,4,6 17,19,21 16,18,20 1,3,5 31,32,33 38,39,40 target genes Inflammatory Signals NF κ B Parameter # Description biochem. genetic pharm. 1,3,5,8,10,12,13,14,15 Association IkB-NFkB b1 16,18,20,23,25,27,28,29,30 Dissociation IkB-NFkB b2 2,4,5,7,9,11 Association IKK-IkB b3 17,19,21,22,24,26 Dissociation IKK-IkB b4 37 Export NFkB b5 LMB 44 Import NFkB b6 31,32,33 Export IkB-NFkB b7
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