Ubiquilin overexpression reduces GFP-polyalanine-induced protein aggregates and toxicity.

Ubiquilin overexpression reduces GFP-polyalanine-induced protein aggregates and toxicity. Research Abstract Details 

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Ubiquilin overexpression reduces GFP-polyalanine-induced protein aggregates and toxicity. Abstract Text:

Hongmin Wang,Mervyn J Monteiro,

Several human disorders are associated with an increase in a continuous stretch of alanine amino acids in proteins. These so-called polyalanine expansion diseases share many similarities with polyglutamine-related disorders, including a length-dependent reiteration of amino acid induction of protein aggregation and cytotoxicity. We previously reported that overexpression of ubiquilin reduces protein aggregates and toxicity of expanded polyglutamine proteins. Here, we demonstrate a similar role for ubiquilin toward expanded polyalanine proteins. Overexpression of ubiquilin-1 in HeLa cells reduced protein aggregates and the cytotoxicity associated with expression of a transfected nuclear-targeted GFP-fusion protein containing 37-alanine repeats (GFP-A37), in a dose dependent manner. Ubiquilin coimmunoprecipitated more with GFP proteins containing a 37-polyalanine tract compared to either 7 (GFP-A7), or no alanine tract (GFP). Moreover, overexpression of ubiquilin suppressed the increased vulnerability of HeLa cell lines stably expressing the GFP-A37 fusion protein to oxidative stress-induced cell death compared to cell lines expressing GFP or GFP-A7 proteins. By contrast, siRNA knockdown of ubiquilin expression in the GFP-A37 cell line was associated with decreased cellular proliferation, and increases in GFP protein aggregates, nuclear fragmentation, and cell death. Our results suggest that boosting ubiquilin levels in cells might provide a universal and attractive strategy to prevent toxicity of proteins containing reiterative expansions of amino acids involved in many human diseases.

Ubiquilin overexpression reduces GFP-polyalanine-induced protein aggregates and toxicity. Publishing Authors By Initials

H Wang,MJ Monteiro,

For similar genetic processes: gene expression regulation: up-regulation research abstracts see: genetic processes: gene expression regulation: up-regulation research

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Ubiquilin overexpression reduces GFP-polyalanine-induced protein aggregates and toxicity. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Experimental cell research

VOLUME: 313

Page Numbers: 2810-20

Journal Abbreviation: Exp. Cell Res.

ISSN: 0014-4827

DAY: 6

MONTH: 04

YEAR: 2007

Ubiquilin overexpression reduces GFP-polyalanine-induced protein aggregates and toxicity. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 373226

Ubiquilin overexpression reduces GFP-polyalanine-induced protein aggregates and toxicity. Keywords Mesh Terms:

KEYWORDS: Up-Regulation

MESH TERMS: drug effects

Chemical & Substance for Abstract: Ubiquilin overexpression reduces GFP-polyalanine-induced protein aggregates and toxicity. Information

Substance Name: Hydrogen Peroxide

Registry Number: 7722-84-1

Grant and Affiliation Information for Ubiquilin overexpression reduces GFP-polyalanine-induced protein aggregates and toxicity.

AFFILIATION: Medical Biotechnology Center, Institute for Neurodegenerative Diseases, University of Maryland Biotechnology Institute, Room N352, Baltimore, MD 21201, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM066287

ACRONYM: GM

MEDLINETA: Exp Cell Res

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