Dorfin localizes to Lewy bodies and ubiquitylates synphilin-1.

Dorfin localizes to Lewy bodies and ubiquitylates synphilin-1. Research Abstract Details 

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Dorfin localizes to Lewy bodies and ubiquitylates synphilin-1. Abstract Text:

Takashi Ito,Jun-Ichi Niwa,Nozomi Hishikawa,Shinsuke Ishigaki,Manabu Doyu,Gen Sobue,

Parkinson's disease (PD) is a neurodegenerative disease characterized by loss of nigra dopaminergic neurons. Lewy bodies (LBs) are a characteristic neuronal inclusion in PD brains. In this study, we report that Dorfin, a RING finger-type ubiquityl ligase for mutant superoxide dismutase-1, was localized with ubiquitin in LBs. Recently, synphilin-1 was identified to associate with alpha-synuclein and to be a major component of LBs. We found that overexpression of synphilin-1 in cultured cells led to the formation of large juxtanuclear inclusions, but showed no cytotoxicity. Dorfin colocalized in these large inclusions with ubiquitin and proteasomal components. In contrast to full-length synphilin-1, overexpression of the central portion of synphilin-1, including ankyrin-like repeats, a coiled-coil domain, and an ATP/GTP-binding domain, predominantly led to the formation of small punctate aggregates scattered throughout the cytoplasm and showed cytotoxic effects. Dorfin and ubiquitin did not localize in these small aggregates. Overexpression of the N or C terminus of synphilin-1 did not lead to the formation of any aggregates. Dorfin physically bound and ubiquitylated synphilin-1 through its central portion, but did not ubiquitylate wild-type or mutant alpha-synuclein. These results suggest that the central domain of synphilin-1 has an important role in the formation of aggregates and cytotoxicity and that Dorfin may be involved in the pathogenic process of PD and LB formation by ubiquitylation of synphilin-1.

Dorfin localizes to Lewy bodies and ubiquitylates synphilin-1. Publishing Authors By Initials

T Ito,J Niwa,N Hishikawa,S Ishigaki,M Doyu,G Sobue,

For similar proteins: nerve tissue proteins: synucleins: alpha-synuclein research abstracts see: proteins: nerve tissue proteins: synucleins: alpha-synuclein research

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Dorfin localizes to Lewy bodies and ubiquitylates synphilin-1. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 278

Page Numbers: 29106-14

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 15

MONTH: 05

YEAR: 2003

Dorfin localizes to Lewy bodies and ubiquitylates synphilin-1. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Dorfin localizes to Lewy bodies and ubiquitylates synphilin-1. Keywords Mesh Terms:

KEYWORDS: alpha-Synuclein

MESH TERMS: metabolism

Chemical & Substance for Abstract: Dorfin localizes to Lewy bodies and ubiquitylates synphilin-1. Information

Substance Name: RNF19A protein, human

Registry Number: EC 6.3.2.-

Grant and Affiliation Information for Dorfin localizes to Lewy bodies and ubiquitylates synphilin-1.

AFFILIATION: Department of Neurology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.

Country: United States

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MEDLINETA: J Biol Chem

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