Intracellular CMTM2 negatively regulates human immunodeficiency virus type-1 transcription through targeting the transcription factors AP-1 and CREB
Intracellular CMTM2 negatively regulates human immunodeficiency virus type-1 transcription through targeting the transcription factors AP-1 and CREB
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DOI：
10.3760/cma.j.issn.0366-6999.2010.17.027
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发表时间：
2010-09-05
影响因子：
6.1
通讯作者：
Zhuang Hui
中科院分区：
文献类型：
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作者：
Song Hong-shuo;Shi Shuang;Zhuang Hui
背景：CKLF样的Marvel跨膜结构域家族(CMTM)是一个连接趋化因子和TM4SF的新蛋白家族。不同的成员具有不同的生物学功能。本研究旨在探讨CMTM2对人类免疫缺陷病毒1型(HIV-1)转录的调控作用。方法采用荧光素酶分析法检测CMTM2对HIV-1前病毒全长及长末端重复序列(LTR)转录的调控作用。利用荧光素酶报告质粒AP-1、Cre和NF-kB进行转录因子分析，以探讨CMTM2可能调控的信号通路(S)。通过Western blotting进一步分析CMTM2与转录因子AP-1之间的关系，探讨CMTM2在PMA诱导的ERK1/2磷酸化中的作用。CMTM2对HIV-1前病毒全长转录和HIV-1 LTR引导的转录均有抑制作用。转录因子分析显示，CMTM2选择性地抑制基础AP-1和CREB活性。结论细胞内CMTM2可通过靶向AP-1和CREB途径，至少部分地负性调节HIV-1转录。进一步探索这些机制可能会带来控制HIV-1复制的新方法。中华医学杂志2010；123(17)：2440-2445
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