Bax-inhibiting peptide protects cells from polyglutamine toxicity caused by Ku70 acetylation.

Bax-inhibiting peptide protects cells from polyglutamine toxicity caused by Ku70 acetylation. Research Abstract Details 

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Bax-inhibiting peptide protects cells from polyglutamine toxicity caused by Ku70 acetylation. Abstract Text:

Y Li,T Yokota,V Gama,T Yoshida,J A Gomez,K Ishikawa,H Sasaguri,H Y Cohen,D A Sinclair,H Mizusawa,S Matsuyama,Y Li,T Yokota,V Gama,T Yoshida,J A Gomez,K Ishikawa,H Sasaguri,H Y Cohen,D A Sinclair,H Mizusawa,S Matsuyama,Y Li,T Yokota,V Gama,T Yoshida,J A Gomez,K Ishikawa,H Sasaguri,H Y Cohen,D A Sinclair,H Mizusawa,S Matsuyama,

Polyglutamine (polyQ) diseases, such as Huntington's disease and Machado-Joseph disease (MJD), are caused by gain of toxic function of abnormally expanded polyQ tracts. Here, we show that expanded polyQ of ataxin-3 (Q79C), a gene that causes MJD, stimulates Ku70 acetylation, which in turn dissociates the proapoptotic protein Bax from Ku70, thereby promoting Bax activation and subsequent cell death. The Q79C-induced cell death was significantly blocked by Ku70 or Bax-inhibiting peptides (BIPs) designed from Ku70. Furthermore, expression of SIRT1 deacetylase and the addition of a SIRT1 agonist, resveratrol, reduced Q79C toxicity. In contrast, mimicking acetylation of Ku70 abolished the ability of Ku70 to suppress Q79C toxicity. These results indicate that Bax and Ku70 acetylation play important roles in Q79C-induced cell death, and that BIP may be useful in the development of therapeutics for polyQ diseases.Cell Death and Differentiation (2007) 14, 2058-2067; doi:10.1038/sj.cdd.4402219; published online 21 September 2007.

Bax-inhibiting peptide protects cells from polyglutamine toxicity caused by Ku70 acetylation. Publishing Authors By Initials

Y Li,T Yokota,V Gama,T Yoshida,JA Gomez,K Ishikawa,H Sasaguri,HY Cohen,DA Sinclair,H Mizusawa,S Matsuyama,Y Li,T Yokota,V Gama,T Yoshida,JA Gomez,K Ishikawa,H Sasaguri,HY Cohen,DA Sinclair,H Mizusawa,S Matsuyama,Y Li,T Yokota,V Gama,T Yoshida,JA Gomez,K Ishikawa,H Sasaguri,HY Cohen,DA Sinclair,H Mizusawa,S Matsuyama,

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Bax-inhibiting peptide protects cells from polyglutamine toxicity caused by Ku70 acetylation. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Cell death and differentiation

VOLUME: 14

Page Numbers: 2058-67

Journal Abbreviation: Cell Death Differ.

ISSN: 1350-9047

DAY: 21

MONTH: 09

YEAR: 2007

Bax-inhibiting peptide protects cells from polyglutamine toxicity caused by Ku70 acetylation. Information

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LANGUAGE: eng

NlmUniqueID: 9437445

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Grant and Affiliation Information for Bax-inhibiting peptide protects cells from polyglutamine toxicity caused by Ku70 acetylation.

AFFILIATION: 1Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan.

Country: England

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MEDLINETA: Cell Death Differ

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