320Fall10Lecture14 - 1 BIO 320 Cell Biology, Fall 2010 Dr....

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BIO 320 Cell Biology, Fall 2010 Dr. Thomas Bushart Week 14 1
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Proteolytic signaling Regulated cleavage of a protein activates or inhibits a signaling pathway I Notch – releases gene regulatory domain that can enter nucleus I Wnt – suppresses degradation of gene regulatory element I NF- κ B – inhibitor of gene regulator is degraded I Hedgehog – processed element suppresses, full protein enhances 2
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Notch Cells fated to become neurons can signal neighbors to not become neurons (lateral inhibition) Glycoproteins I Delta signal I Notch receptor Notch fragment converts a DNA binding protein from a gene repressor to a gene activator 3
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Notch processing 4
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Alzheimer’s and proteolysis β -amyloid percursor protein (APP) is expressed in neurons Presenilin-1 (PS-1) participates in the Notch cleavage I Component of γ -secretase Hyperactive PS-1 increases the rate of APP cleavage in transmembrane region I Releases cytoplasmic and extracellular fragements I Accumulation of extracellular APP fragements results in nerve-damaging amyloid plaques 5
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Wnt signals and Frizzled receptors Frizzled receptors are seven-pass transmembrane proteins I Major signaling pathway is NOT through G proteins I Wnt binding requires an LDL-receptor-related protein (LRP) I Acts through Dishevelled cytoplasmic signaling protein I β -catenin is the proteolysis target Protein normally stably associated with adheren junctions 6
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β -catenin processing 7
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Cancer and Wnt/ β -catenin Mutations in APC (Adenomatous polyposis coli) allow accumulation of β -catenin and production of Myc 8
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Hedgehog signaling Depends on three transmembrane proteins 9
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This note was uploaded on 12/30/2010 for the course BIO 320 taught by Professor Staff during the Spring '08 term at University of Texas at Austin.

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320Fall10Lecture14 - 1 BIO 320 Cell Biology, Fall 2010 Dr....

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