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学科主题: 基础医学
题名:
Intracellular CMTM2 negatively regulates human immunodeficiency virus type-1 transcription through targeting the transcription factors AP-1 and CREB
作者: Song Hong-shuo1; Shi Shuang1; Lu Xiao-zhi3; Gao Feng3; Yan Ling1; Wang Ying2; Zhuang Hui1
关键词: CMTM2 ; HIV-1 ; long terminal repeat ; regulation
刊名: CHINESE MEDICAL JOURNAL
发表日期: 2010-09-05
DOI: 10.3760/cma.j.issn.0366-6999.2010.17.027
卷: 123, 期:17, 页:2440-2445
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, General & Internal
研究领域[WOS]: General & Internal Medicine
关键词[WOS]: SER(133) PHOSPHORYLATION ; MOLECULAR-CLONING ; CELLS ; INFECTION ; PROMOTER ; GENE ; CAMP ; ACTIVATION ; CYTOKINE ; CKLFSF2
英文摘要:

Background The CKLF-like MARVEL transmembrane domain-containing family (CMTM) is a novel family of proteins linking chemokines and TM4SF. Different members exhibit diverse biological functions. In this study, the effect of intracellular CMTM2 on regulating human immunodeficiency virus type-1 (HIV-1) transcription was evaluated.

Methods The effects of CMTM2 on regulating full-length HIV-1 provirus and the HIV-1 long terminal repeat (LTR)-directed transcription were assessed by luciferase assay. Transcription factor assays, using the luciferase reporter plasmids of AP-1, CRE, and NF-kB were conducted to explore the signaling pathway(s) that may be regulated by CMTM2. The potential relationship between CMTM2 and the transcription factor AP-1 was further analyzed by Western blotting analyses to investigate the effect of CMTM2 on PMA-induced ERK1/2 phosphorylation.

Results The results from the current study revealed that CMTM2 acts as a negative regulator of HIV-1 transcription. CMTM2 exerted a suppressive action on both full-length HIV-1 provirus and HIV-1 LTR-directed transcription. Transcription factor assays showed that CMTM2 selectively inhibited basal AP-1 and CREB activity. Co-expression of HIV-1 Tat, a potent AP-1 and CREB activator, can not reverse CMTM2-mediated AP-1 and CREB inhibition, suggesting a potent and specific effect of CMTM2 on negatively regulating these two signaling pathways.

Conclusion Intracellular CMTM2 can negatively regulate HIV-1 transcription, at least in part, by targeting the AP-1 and CREB pathways. Exploring the mechanisms further may lead to new ways to control HIV-1 replication. Chin Med J 2010;123(17):2440-2445

语种: 英语
所属项目编号: 30600562
项目资助者: National Natural Sciences Foundation of China
WOS记录号: WOS:000282153900027
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58901
Appears in Collections:基础医学院_病原生物学系_期刊论文

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作者单位: 1.Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA
2.Peking Univ, Dept Microbiol, Hlth Sci Ctr, Beijing 100191, Peoples R China
3.Peking Univ, Dept Immunol, Hlth Sci Ctr, Beijing 100191, Peoples R China

Recommended Citation:
Song Hong-shuo,Shi Shuang,Lu Xiao-zhi,et al. Intracellular CMTM2 negatively regulates human immunodeficiency virus type-1 transcription through targeting the transcription factors AP-1 and CREB[J]. CHINESE MEDICAL JOURNAL,2010,123(17):2440-2445.
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