Parkin substrate and assay

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or...

Reexamination Certificate

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Reexamination Certificate

active

08062839

ABSTRACT:
The invention provides in vitro, ex vivo, and in vivo assays for Parkin activity, in which Parkin-mediated ubiquitination of a Sept4 protein is measured. The assays may be used to screen for agents that modulate Parkin protein ligase activity.

REFERENCES:
patent: 2004/0214763 (2004-10-01), Corti et al.
patent: 2008/0293089 (2008-11-01), Johnston et al.
patent: 1 416 272 (2004-05-01), None
patent: WO 2008/144736 (2008-11-01), None
Choi et al. “SEPT5—v2 is a parkin-binding protein”, Molecular Brain Research, 2003, 117:179-189.
Hampe et al. “Biochemical analysis of Parkinson's disease-causing variants of Parkin, an E3 ubiquitin-protein ligase with monoubiquitylation capacity”, Human Molecular Genetics, 2006, 15(13):2059-2075.
U.S. Appl. No. 60/939,335, filed May 21, 2007, Johnston.
Hershko et al., “The Ubiquitin System,”Annual Review of Biochemistry, 67:425-479 (1998).
Hicke, “Getting' Down With Ubiquitin: Turning of Cell-Surface Receptors, Transporters and Channels,” Trends in Cell Biology, 9:107-112 (1999).
Ihara et al., “Association of the Cytoskeletal GTP-binding Protein Sept4/H5 with Cytoplasmic Inclusions Found in Parkinson's Disease and other Synucleinopathies,”Journal of Biological Chemistry, 278(26):24095-24102 (2003).
Ihara et al., “Sept4, a Component of Presynaptic Scaffold and Lewy Bodies, is Required for the Suppression of Alpha-Synuclein Neurotoxicity,”Neuron, 53(4):519-533 (2007).
Imai et al., “An Unfolded Putative Transmembrane Polypeptide, which can Lead to Endoplasmic Reticulum Stress, is a Substrate of Parkin,”Cell, 105(7):891-902 (2001).
Larisch et al., “A Novel Mitochondrial Septin-Like Protein, ARTS, Mediates Apoptosis Dependent on its P-loop Motif,”Nature Biology, 2:915-921 (2000).
PCT Search Report of Jun. 23, 2008 for application PCT/US2008/064372.
Periquet et al., “Proteomic Analysis of Parkin Knockout Mice: Alterations in Energy Metabolism, Protein Handling and Synaptic Function,”Journal of Neurochemistry, 95(5):1259-1276 (2005).
Sawkar et al., “Chemical chaperones and Permissive Temperatures Alter the Cellular Localization of Gaucher Disease Associated Glucocerebrosidase Variants,”ACS Chemical Biology, 1(4):235-251 (2006).

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