|Intracellular CMTM2 negatively regulates human immunodeficiency virus type-1 transcription through targeting the transcription factors AP-1 and CREB|
|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|
|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|
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
|资助机构||National Natural Sciences Foundation of China|
|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
|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.|
|APA||Song Hong-shuo.,Shi Shuang.,Lu Xiao-zhi.,Gao Feng.,Yan Ling.,...&Zhuang Hui.(2010).Intracellular CMTM2 negatively regulates human immunodeficiency virus type-1 transcription through targeting the transcription factors AP-1 and CREB.CHINESE MEDICAL JOURNAL,123(17),2440-2445.|
|MLA||Song Hong-shuo,et al."Intracellular CMTM2 negatively regulates human immunodeficiency virus type-1 transcription through targeting the transcription factors AP-1 and CREB".CHINESE MEDICAL JOURNAL 123.17(2010):2440-2445.|
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