Modulation of Abeta generation by small ubiquitin-like modifiers does not require conjugation to target proteins.

Modulation of Abeta generation by small ubiquitin-like modifiers does not require conjugation to target proteins. Research Abstract Details 

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Modulation of Abeta generation by small ubiquitin-like modifiers does not require conjugation to target proteins. Abstract Text:

Dorval,Matthew J Mazzella,Paul M Mathews,Ronald T Hay,Paul E Fraser,

The sequential processing of the APP (amyloid precursor protein) by the beta- and gamma-secretase and generation of the Abeta (amyloid-beta) peptide is a primary pathological factor in AD (Alzheimer's disease). Regulation of the processing or turnover of these proteins represents potential targets for the development of AD therapies. Sumoylation is a process by which SUMOs (small ubiquitin-like modifiers) are covalently conjugated to target proteins, resulting in a number of functional consequences. These include regulation of protein-protein interactions, intracellular trafficking and protein stability, which all have the potential to impact on several aspects of the amyloidogenic pathway. The present study examines the effects of overexpression and knockdown of the major SUMO isoforms (SUMO1, 2 and 3) on APP processing and the production of Abeta peptides. SUMO3 overexpression significantly increased Abeta40 and Abeta42 secretion, which was accompanied by an increase in full-length APP and its C-terminal fragments. These effects of SUMO3 were independent of its covalent attachment or chain formation, as mutants lacking the motifs responsible for SUMO chain formation or SUMO conjugation led to similar changes in Abeta. SUMO3 overexpression also up-regulated the expression of the transmembrane protease BACE (beta-amyloid-cleaving enzyme), but failed to affect levels of several other unrelated proteins. Suppression of SUMO1 or combined SUMO2+3 by RNA interference did not affect APP levels or Abeta production. These findings confirm a specific effect of SUMO3 overexpression on APP processing and the production of Abeta peptides but also suggest that endogenous sumoylation is not essential and likely plays an indirect role in modulating the amyloid processing pathway.

Modulation of Abeta generation by small ubiquitin-like modifiers does not require conjugation to target proteins. Publishing Authors By Initials

V Dorval,MJ Mazzella,PM Mathews,RT Hay,PE Fraser,

For similar proteins: ubiquitins: ubiquitin research abstracts see: proteins: ubiquitins: ubiquitin research

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Modulation of Abeta generation by small ubiquitin-like modifiers does not require conjugation to target proteins. Journal Published:

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

Journal: The Biochemical journal

VOLUME: 404

Page Numbers: 309-16

Journal Abbreviation: Biochem. J.

ISSN: 1470-8728

DAY: 1

MONTH: Jun

YEAR: 2007

Modulation of Abeta generation by small ubiquitin-like modifiers does not require conjugation to target proteins. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2984726

Modulation of Abeta generation by small ubiquitin-like modifiers does not require conjugation to target proteins. Keywords Mesh Terms:

KEYWORDS: Ubiquitin

MESH TERMS: metabolism

Chemical & Substance for Abstract: Modulation of Abeta generation by small ubiquitin-like modifiers does not require conjugation to target proteins. Information

Substance Name: Ubiquitin

Registry Number: 0

Grant and Affiliation Information for Modulation of Abeta generation by small ubiquitin-like modifiers does not require conjugation to target proteins.

AFFILIATION: Department of Medical Biophysics and Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada, M5S 3HZ. veronique.dorval@utoronto.ca

Country: England

AGENCY: United States NINDS

GRANT: NS45357

ACRONYM: NS

MEDLINETA: Biochem J

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