PMID:16461359

Citation	Qin, Q, Inatome, R, Hotta, A, Kojima, M, Yamamura, H, Hirai, H, Yoshizawa, T, Tanaka, H, Fukami, K and Yanagi, S (2006) A novel GTPase, CRAG, mediates promyelocytic leukemia protein-associated nuclear body formation and degradation of expanded polyglutamine protein. J. Cell Biol. 172:497-504
Abstract	Polyglutamine diseases are inherited neurodegenerative diseases caused by the expanded polyglutamine proteins (polyQs). We have identified a novel guanosine triphosphatase (GTPase) named CRAG that contains a nuclear localization signal (NLS) sequence and forms nuclear inclusions in response to stress. After ultraviolet irradiation, CRAG interacted with and induced an enlarged ring-like structure of promyelocytic leukemia protein (PML) body in a GTPase-dependent manner. Reactive oxygen species (ROS) generated by polyQ accumulation triggered the association of CRAG with polyQ and the nuclear translocation of the CRAG-polyQ complex. Furthermore, CRAG promoted the degradation of polyQ at PML/CRAG bodies through the ubiquitin-proteasome pathway. CRAG knockdown by small interfering RNA in neuronal cells consistently blocked the nuclear translocation of polyQ and enhanced polyQ-mediated cell death. We propose that CRAG is a modulator of PML function and dynamics in ROS signaling and is protectively involved in the pathogenesis of polyglutamine diseases.
Links	PubMed PMC2063670 Online version:10.1083/jcb.200505079
Keywords	Amino Acid Sequence; Animals; Cells, Cultured; GTP Phosphohydrolases/genetics; GTP Phosphohydrolases/metabolism; HeLa Cells; Humans; Intranuclear Inclusion Bodies/metabolism; Mice; Molecular Sequence Data; Neoplasm Proteins/genetics; Neoplasm Proteins/metabolism; Nuclear Localization Signals/genetics; Nuclear Localization Signals/metabolism; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Peptides/metabolism; Rats; Transcription Factors/genetics; Transcription Factors/metabolism; Tumor Suppressor Proteins/genetics; Tumor Suppressor Proteins/metabolism; Ubiquitin-Activating Enzymes/metabolism; Ubiquitin-Conjugating Enzymes/metabolism; Ultraviolet Rays
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:PML	located_in	GO:0016605: PML body	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:AGAP3	acts_upstream_of_or_within	GO:0034614: cellular response to reactive oxygen species	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:AGAP3	located_in	GO:0005634: nucleus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:AGAP3	located_in	GO:0005737: cytoplasm	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:AGAP3	acts_upstream_of_or_within	GO:0006606: protein import into nucleus	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:AGAP3	enables	GO:0031593: polyubiquitin modification-dependent protein binding	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
MOUSE:AGAP3	enables	GO:0003924: GTPase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
MOUSE:AGAP3	located_in	GO:0071944: cell periphery	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:AGAP3	acts_upstream_of_or_within	GO:0043161: proteasome-mediated ubiquitin-dependent protein catabolic process	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:PML	part_of	GO:0016605: PML body	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete

References

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