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学科主题: 临床医学
题名:
The Tumor Suppressor, p53 Regulates the gamma A-Crystallin Gene During Mouse Lens Development
作者: Hu, X. -H.1,2; Nie, Q.1; Yi, M.1; Li, T. -T.1,2; Wang, Z. -F.2,3; Huang, Z. -X.1,2; Gong, X. -D.1; Zhou, L.1; Ji, W. -K.2; Hu, W. -F.1,2; Liu, J. -F.2,4,5; Wang, L.1,2; Woodward, Z.2; Zhu, J.3; Liu, W. -B.1; Nguyen, Q. D.2; Li, D. W. -C.1,2
关键词: Cataract ; gamma A-crystallin gene ; gene regulation ; lens differentiation ; p53
刊名: CURRENT MOLECULAR MEDICINE
发表日期: 2014
卷: 14, 期:9, 页:1197-1204
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]: FIBER CELL-DIFFERENTIATION ; ALPHA-B-CRYSTALLIN ; WILD-TYPE P53 ; TRANSCRIPTION FACTOR ; P53-DEPENDENT APOPTOSIS ; C-MAF ; EPITHELIAL-CELLS ; CYCLE ARREST ; EXPRESSION ; PROTEIN
英文摘要:

The tumor suppressor, p53 regulates a large number of target genes to control cell proliferation and apoptosis. In addition, it is also implicated in the regulation of cell differentiation in muscle, the circulatory system and various carcinoma tissues. We have recently shown that p53 also controls lens differentiation. Regarding the mechanism, we reveal that p53 directly regulates several genes including c-Maf and Prox1, two important transcription factors for lens differentiation, and alpha A and beta A3/A1, the lens differentiation markers. In the present study, we present evidence to show that the gamma A-crystallin gene distal promoter and the first intron also contain p53 binding sites and are capable of mediating p53 control during mouse lens development. First, gel mobility shifting assays revealed that the p53 protein in nuclear extracts from human lens epithelial cells (HLE) directly binds to the p53 binding sites present in the gamma A-crystallin gene. Second, the exogenous wild type p53 induces the dose-dependent expression of the luciferase reporter gene driven by the basic promoter containing the gamma A-crystallin gene p53 binding site. In contrast, the exogenous dominant negative mutant p53 causes a dose-dependent inhibition of the same promoter. Third, ChIP assays revealed that p53 binds to the gamma A-crystallin gene promoter in vivo. Finally, in the p53 knockout mouse lenses, the expression level of the gamma A-crystallin gene was found attenuated in comparison with that in the wild type mouse lenses. Together, our results reveal that p53 regulates gamma A-crystallin gene expression during mouse lens development. Thus, p53 directly regulates all 3 types of crystallin genes to control lens differentiation.

语种: 英语
所属项目编号: 1R01EY018380 ; 81272228 ; 20134486
项目资助者: National Institute of Health ; National Natural Science Foundation of China ; Cooperative Innovation Center of Engineering and New Products for Developmental Biology of Hunan Province ; Hunan Normal University ; Chinese Scholarship Council
WOS记录号: WOS:000345223700008
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52595
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: 1.Hunan Normal Univ, Coll Life Sci, Key Lab Prot Chem & Dev Biol, Educ Minist China, Changsha 410081, Hunan, Peoples R China
2.Univ Nebraska, Med Ctr, Stanley M Truhlsen Eye Inst, Dept Ophthalmol & Visual Sci, Omaha, NE 68198 USA
3.Peking Univ, Peoples Hosp, Hepatobiliary Surg Ctr, Beijing 100044, Peoples R China
4.Guangzhou Med Univ, Canc Res Inst, Guangzhou 510095, Guangdong, Peoples R China
5.Guangzhou Med Univ, Canc Hosp, Guangzhou 510095, Guangdong, Peoples R China

Recommended Citation:
Hu, X. -H.,Nie, Q.,Yi, M.,et al. The Tumor Suppressor, p53 Regulates the gamma A-Crystallin Gene During Mouse Lens Development[J]. CURRENT MOLECULAR MEDICINE,2014,14(9):1197-1204.
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