Intracellular CMTM2 negatively regulates human immunodeficiency virus type-1 transcription through targeting the transcription factors AP-1 and CREB / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 2440-2445, 2010.
Article
in En
| WPRIM
| ID: wpr-237436
Responsible library:
WPRO
ABSTRACT
<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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-κB 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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>
Full text:
1
Index:
WPRIM
Main subject:
Pharmacology
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Physiology
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Transcription, Genetic
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Tetradecanoylphorbol Acetate
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HIV Long Terminal Repeat
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HIV-1
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Cyclic AMP Response Element-Binding Protein
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Transcription Factor AP-1
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Chemokines
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Jurkat Cells
Limits:
Humans
Language:
En
Journal:
Chinese Medical Journal
Year:
2010
Type:
Article