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题名: HSF4 regulates DLAD expression and promotes lens de-nucleation
作者: Cui, Xiukun1; Wang, Lei1; Zhang, Jing1, 2; Du, Rong3; Liao, Shengjie1; Li, Duanzhuo1; Li, Chang1; Ke, Tie1; Li, David Wan-Cheng4, 5; Huang, Hua6; Yin, Zhan2; Tang, Zhaohui1; Liu, Mugen1
通讯作者: Tang, ZH (reprint author), Huazhong Univ Sci & Technol, Ctr Human Genome Res, 1037 Luoyu Rd, Wuhan 430074, Hubei, Peoples R China.
关键词: HSF4 ; Cataract mutation ; DLAD ; Lens differentiation
刊名: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
发表日期: 2013-08-01
DOI: 10.1016/j.bbadis.2013.03.007
卷: 1832, 期:8, 页:1167-1172
收录类别: SCI
文章类型: Article
部门归属: [Cui, Xiukun ; Wang, Lei ; Zhang, Jing ; Liao, Shengjie ; Li, Duanzhuo ; Li, Chang ; Ke, Tie ; Tang, Zhaohui ; Liu, Mugen] Huazhong Univ Sci & Technol, Ctr Human Genome Res, Coll Life Sci & Technol, Key Lab Mol Biophys,Minist Educ, Wuhan 430074, Hubei, Peoples R China ; [Zhang, Jing ; Yin, Zhan] Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China ; [Du, Rong] Huazhong Univ Sci & Technol, Union Hosp, Wuhan 430022, Hubei, Peoples R China ; [Li, David Wan-Cheng] Univ Nebraska Med Ctr, Coll Med, Dept Biochem & Mol Biol, Omaha, NE 68198 USA ; [Li, David Wan-Cheng] Univ Nebraska Med Ctr, Coll Med, Dept Ophthalmol & Visual Sci, Omaha, NE 68198 USA ; [Huang, Hua] Hubei Univ Nationalities, Affiliated Hosp, Enshi 445000, Hubei, Peoples R China
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: National Natural Science Foundation of China [81270983, 31071106, 30771199]; National Key Technology R&D Program of China [2012BAI09B00]; NIH/NEI [1R01EY018380]
类目[WOS]: Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
摘要: HSF4 mutations lead to both congenital and age-related cataract. The purpose of this study was to explore the mechanism of cataract formation caused by HSF4 mutations. The degradation of nuclear DNA is essential for the lens fiber differentiation. DNase 2 beta (DLAD) is highly expressed in lens cells, and mice with deficiencies in the DLAD gene develop nuclear cataracts. In this study, we found that HSF4 promoted the expression and DNase activity of DIAD by directly binding to the DIAD promoter. In contrast, HSF4 cataract causative mutations failed to bind to the DLAD promoter, abrogating the expression and DNase activity of DLAD. These results were confirmed by HSF4 knockdown in zebrafish, which led to incomplete de-nucleation of the lens and decreased expression and activity of DLAD. Together, our results suggest that HSF4 exerts its function on lens differentiation via positive regulation of DIAD expression and activity, thus facilitating de-nucleation of lens fiber cells. Our demonstration that HSF4 cataract causative mutations abrogate the induction of DLAD expression reveals a novel molecular mechanism regarding how HSF4 mutations cause cataractogenesis. (C) 2013 Elsevier B.V. All rights reserved.
英文摘要: HSF4 mutations lead to both congenital and age-related cataract. The purpose of this study was to explore the mechanism of cataract formation caused by HSF4 mutations. The degradation of nuclear DNA is essential for the lens fiber differentiation. DNase 2 beta (DLAD) is highly expressed in lens cells, and mice with deficiencies in the DLAD gene develop nuclear cataracts. In this study, we found that HSF4 promoted the expression and DNase activity of DIAD by directly binding to the DIAD promoter. In contrast, HSF4 cataract causative mutations failed to bind to the DLAD promoter, abrogating the expression and DNase activity of DLAD. These results were confirmed by HSF4 knockdown in zebrafish, which led to incomplete de-nucleation of the lens and decreased expression and activity of DLAD. Together, our results suggest that HSF4 exerts its function on lens differentiation via positive regulation of DIAD expression and activity, thus facilitating de-nucleation of lens fiber cells. Our demonstration that HSF4 cataract causative mutations abrogate the induction of DLAD expression reveals a novel molecular mechanism regarding how HSF4 mutations cause cataractogenesis. (C) 2013 Elsevier B.V. All rights reserved.
关键词[WOS]: RECESSIVE CONGENITAL CATARACTS ; FIBER CELL-DIFFERENTIATION ; HEAT-SHOCK RESPONSE ; ALPHA-B-CRYSTALLIN ; MOUSE EYE LENS ; DNASE-II ; TRANSCRIPTION FACTOR ; MUTATION ; DEGRADATION ; FAMILY
语种: 英语
WOS记录号: WOS:000321081300007
ISSN号: 0925-4439
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/19612
Appears in Collections:水生生物分子与细胞生物学研究中心_期刊论文

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作者单位: 1.Huazhong Univ Sci & Technol, Ctr Human Genome Res, Coll Life Sci & Technol, Key Lab Mol Biophys,Minist Educ, Wuhan 430074, Hubei, Peoples R China
2.Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China
3.Huazhong Univ Sci & Technol, Union Hosp, Wuhan 430022, Hubei, Peoples R China
4.Univ Nebraska Med Ctr, Coll Med, Dept Biochem & Mol Biol, Omaha, NE 68198 USA
5.Univ Nebraska Med Ctr, Coll Med, Dept Ophthalmol & Visual Sci, Omaha, NE 68198 USA
6.Hubei Univ Nationalities, Affiliated Hosp, Enshi 445000, Hubei, Peoples R China

Recommended Citation:
Cui, Xiukun; Wang, Lei; Zhang, Jing; Du, Rong; Liao, Shengjie; Li, Duanzhuo; Li, Chang; Ke, Tie; Li, David Wan-Cheng; Huang, Hua; Yin, Zhan; Tang, Zhaohui; Liu, Mugen.HSF4 regulates DLAD expression and promotes lens de-nucleation,BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,2013,1832(8):1167-1172
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