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学科主题基础医学
Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration
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
2011-12-01
DOI10.1002/emmm.201100180
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
WOS记录号WOS:000297694500007
引用统计
被引频次:34[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66446
专题北京大学基础医学院_免疫学系
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
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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.
APA Siudeja, Katarzyna.,Srinivasan, Balaji.,Xu, Lanjun.,Rana, Anil.,de Jong, Jannie.,...&Sibon, Ody C. M..(2011).Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration.EMBO MOLECULAR MEDICINE,3(12),755-766.
MLA Siudeja, Katarzyna,et al."Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration".EMBO MOLECULAR MEDICINE 3.12(2011):755-766.
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