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学科主题: 临床医学
题名:
Identification of novel alternative splicing variants of interferon regulatory factor 3
作者: Li, Yong; Hu, Xiuhua; Song, Yuqin; Lu, Zheming; Ning, Tao; Cai, Hong; Ke, Yang
关键词: IRF-3 ; IRF-3a ; IFN beta ; Splicing variant ; Cancer
刊名: BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
发表日期: 2011-03-01
DOI: 10.1016/j.bbagrm.2011.01.006
卷: 1809, 期:3, 页:166-175
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]: Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]: STIMULATED RESPONSE ELEMENT ; GENE-EXPRESSION ; HUMAN-PAPILLOMAVIRUS ; TRANSCRIPTION FACTORS ; IRF-3 ACTIVATION ; VIRUS-INFECTION ; DNA-BINDING ; CANCER ; COMPLEX ; PROTEIN
英文摘要:

Interferon regulatory factor 3 (IRF-3) plays a crucial role in host defense against viral and microbial infection as well as in cell growth regulation. IRF-3a is the only structurally and functionally characterized IRF-3 splicing variant and has been established to antagonize IRF-3 activity. Here, five novel splicing variants of IRF-3, referred to as IRF-3b, -3c, -3d, -3e, and -3f, were identified and shown to be generated by deletion of exons 2, 3, or 6 or some combination thereof. RT-PCR examination revealed that these novel splicing variants were more frequently expressed in human liver, esophagus, and cervical tumor tissues than in their normal counterparts. Additionally, electrophoretic mobility shift assay and subcellular localization showed only IRF-3 and IRF-3e were capable of binding the PRDI/III element of interferon-beta (IFN beta) promoter in vitro and underwent cytoplasm-to-nucleus translocation following Poly(I:C) stimulation. Coimmunoprecipitation assay revealed that only IRF-3c (3f) of novel splicing variants associated with IRF-3 in vivo. Further luciferase assay showed IRF-3c (3f) and IRF-3e failed to transactivate PRDI/III-containing promoter but appeared to inhibit transactivation potential of IRF-3 to varying degrees. Taken together, our findings suggest novel splicing variants may function as negative modulators of IRF-3 and may be correlated with pathogenesis of human tumors. (C) 2011 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 2002AA00110 ; 2002BA711A06 ; 1998051203 ; 30400526 ; 30871366 ; 5061002 ; 5092009
项目资助者: National Ministry of Science and Technology ; Chinese National "973" basic project ; National Natural Science Foundation of China ; Beijing Municipal Natural Science Foundations
WOS记录号: WOS:000289138200002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51600
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: Peking Univ, Sch Oncol, Beijing Canc Hosp & Inst,Dept Genet, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100142, Peoples R China

Recommended Citation:
Li, Yong,Hu, Xiuhua,Song, Yuqin,et al. Identification of novel alternative splicing variants of interferon regulatory factor 3[J]. BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS,2011,1809(3):166-175.
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