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AssigneeExelixis, Inc.
InventorsDaniel Tim Curtis, George Ross Francis, Michael Christopher Ellis, David Andrew Ruddy, Sharmon Monique Nicoll, Garth Joseph McGrath
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The invention provides methods and compositions relating to pen polypeptides having pen-specific structure and activity, related polynucleotides and modulators of pen function. The invention provides isolated pen hybridization probes and primers capable of specifically hybridizing with natural pen genes, pen-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis (e.g. genetic hybridization screens for pen transcripts), therapy (e.g. pen inhibitors to modulate APP processing) and in the biopharmaceutical industry (e.g. as immunogens, reagents for screening chemical libraries for lead pharmacological agents, etc.).
A method for specifically detecting a stress that alters a functional interaction of a presenilin enhancer (pen) polypeptide with Notch processing or with amyloid precursor protein (APP) processing in a C. elegans cell in situ which provides a functional interaction of a pen polypeptide with Notch or APP processing, wherein the stress is a modulator of Notch or APP processing, wherein the pen polypeptide comprises a wild-type pen selected from the group consisting of C. elegans (SEQ ID NO:7) Pen-2 and C. elegans (SEQ ID NO:1) Pen-1, wherein said cell is stressed by a disruption of a pen gene function, said disruption sufficient to provide a sensitized Notch or APP processing pathway, the method comprising steps:
A method for specifically detecting a stress that alters a functional interaction of a presenilin enhancer (pen) polypeptide with amyloid precursor protein (APP) processing, in a C. elegans cell in situ, wherein the stress is a modulator of APP processing, wherein said cell is stressed by disrupting a pen gene function, said cell providing a functional interaction of a pen polypeptide with APP processing, said disruption sufficient to provide a sensitized APP processing pathway, wherein the pen polypeptide comprises a wild-type pen selected from the group consisting of C. elegans (SEQ ID NO:7) Pen-2, C. elegans (SEQ ID NO:1) Pen-1, and C. elegans (SEQ ID NO:13) Aph-2, the method comprising steps:
A method for specifically detecting a stress that alters a functional interaction of a presenilin enhancer (pen) polypeptide with Notch processing or with amyloid precursor protein (APP) processing in a C. elegans cell in situ which provides a functional interaction of a pen polypeptide with Notch or APP processing, wherein the stress is a modulator of Notch or APP processing, wherein the pen polypeptide comprises a wild-type pen selected from the group consisting of C. elegans (SEQ ID NO:7) Pen-2 and C. elegans (SEQ ID NO:1) Pen-1, wherein said cell is stressed by a disruption of a pen gene function, said disruption sufficient to provide a sensitized Notch or APP processing pathway, the method comprising steps:
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