北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 基础医学院  > 免疫学系  > 期刊论文
学科主题: 基础医学
题名:
Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration
作者: Siudeja, Katarzyna1; Srinivasan, Balaji1; Xu, Lanjun1,2; Rana, Anil1; de Jong, Jannie1; Nollen, Ellen A. A.3; Jackowski, Suzanne4; Sanford, Lynn5; Hayflick, Susan5; Sibon, Ody C. M.1
关键词: DNA damage ; HDAC inhibitors ; NBIA ; PKAN ; protein acetylation
刊名: EMBO MOLECULAR MEDICINE
发表日期: 2011-12-01
DOI: 10.1002/emmm.201100180
卷: 3, 期:12, 页:755-766
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, Research & Experimental
研究领域[WOS]: Research & Experimental Medicine
关键词[WOS]: ALPHA-TUBULIN ; LYSINE 56 ; ACETYLTRANSFERASE ; TRANSCRIPTION ; DEACETYLATION ; SYNTHETASE ; COMPLEXES ; MAMMALS ; REPAIR ; BREAKS
英文摘要:

Pantothenate kinase-associated neurodegeneration (PKAN is a neurodegenerative disease with unresolved pathophysiology. Previously, we observed reduced Coenzyme A levels in a Drosophila model for PKAN. Coenzyme A is required for acetyl-Coenzyme A synthesis and acyl groups from the latter are transferred to lysine residues of proteins, in a reaction regulated by acetyltransferases. The tight balance between acetyltransferases and their antagonistic counterparts histone deacetylases is a well-known determining factor for the acetylation status of proteins. However, the influence of Coenzyme A levels on protein acetylation is unknown. Here we investigate whether decreased levels of the central metabolite Coenzyme A induce alterations in protein acetylation and whether this correlates with specific phenotypes of PKAN models. We show that in various organisms proper Coenzyme A metabolism is required for maintenance of histone- and tubulin acetylation, and decreased acetylation of these proteins is associated with an impaired DNA damage response, decreased locomotor function and decreased survival. Decreased protein acetylation and the concurrent phenotypes are partly rescued by pantethine and HDAC inhibitors, suggesting possible directions for future PKAN therapy development.

语种: 英语
项目资助者: VIDI ; VICI (Dutch organization for scientific research) ; GUIDE (Groningen Graduate school)
WOS记录号: WOS:000297694500007
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66446
Appears in Collections:基础医学院_免疫学系_期刊论文

Files in This Item:
File Name/ File Size Content Type Version Access License
emmm0003-0755.pdf(937KB)期刊论文出版稿限制开放 联系获取全文

作者单位: 1.Univ Groningen, Univ Med Ctr Groningen, Dept Cell Biol Radiat & Stress Cell Biol, Groningen, Netherlands
2.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Lab Med Immunol, Beijing 100871, Peoples R China
3.Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands
4.St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA
5.Oregon Hlth & Sci Univ, Dept Mol & Med Genet Pediat & Neurol, Portland, OR 97201 USA

Recommended Citation:
Siudeja, Katarzyna,Srinivasan, Balaji,Xu, Lanjun,et al. Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration[J]. EMBO MOLECULAR MEDICINE,2011,3(12):755-766.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Siudeja, Katarzyna]'s Articles
[Srinivasan, Balaji]'s Articles
[Xu, Lanjun]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Siudeja, Katarzyna]‘s Articles
[Srinivasan, Balaji]‘s Articles
[Xu, Lanjun]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace