Intracellular CMTM2 negatively regulates human immunodeficiency virus type-1 transcription through targeting the transcription factors AP-1 and CREB

被引:12
|
作者
Song Hong-shuo [1 ]
Shi Shuang [1 ]
Lu Xiao-zhi [3 ]
Gao Feng [3 ]
Yan Ling [1 ]
Wang Ying [2 ]
Zhuang Hui [1 ]
机构
[1] Peking Univ, Dept Microbiol, Hlth Sci Ctr, Beijing 100191, Peoples R China
[2] Peking Univ, Dept Immunol, Hlth Sci Ctr, Beijing 100191, Peoples R China
[3] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA
关键词
CMTM2; HIV-1; long terminal repeat; regulation; SER(133) PHOSPHORYLATION; MOLECULAR-CLONING; CELLS; INFECTION; PROMOTER; GENE; CAMP; ACTIVATION; CYTOKINE; CKLFSF2;
D O I
10.3760/cma.j.issn.0366-6999.2010.17.027
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
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
引用
收藏
页码:2440 / 2445
页数:6
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