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

Publication ,  Journal Article
Song, H-S; Shi, S; Lu, X-Z; Gao, F; Yan, L; Wang, Y; Zhuang, H
Published in: Chin Med J (Engl)
September 2010

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-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. 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.

Duke Scholars

Published In

Chin Med J (Engl)

EISSN

2542-5641

Publication Date

September 2010

Volume

123

Issue

17

Start / End Page

2440 / 2445

Location

China

Related Subject Headings

  • U937 Cells
  • Transcription, Genetic
  • Transcription Factor AP-1
  • Tetradecanoylphorbol Acetate
  • Oncology & Carcinogenesis
  • MARVEL Domain-Containing Proteins
  • Jurkat Cells
  • Intracellular Space
  • Humans
  • HIV-1
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Song, H.-S., Shi, S., Lu, X.-Z., Gao, F., Yan, L., Wang, Y., & Zhuang, H. (2010). Intracellular CMTM2 negatively regulates human immunodeficiency virus type-1 transcription through targeting the transcription factors AP-1 and CREB. Chin Med J (Engl), 123(17), 2440–2445.
Song, Hong-shuo, Shuang Shi, Xiao-zhi Lu, Feng Gao, Ling Yan, Ying Wang, and Hui Zhuang. “Intracellular CMTM2 negatively regulates human immunodeficiency virus type-1 transcription through targeting the transcription factors AP-1 and CREB.Chin Med J (Engl) 123, no. 17 (September 2010): 2440–45.
Song H-S, Shi S, Lu X-Z, Gao F, Yan L, Wang Y, et al. Intracellular CMTM2 negatively regulates human immunodeficiency virus type-1 transcription through targeting the transcription factors AP-1 and CREB. Chin Med J (Engl). 2010 Sep;123(17):2440–5.
Song H-S, Shi S, Lu X-Z, Gao F, Yan L, Wang Y, Zhuang H. Intracellular CMTM2 negatively regulates human immunodeficiency virus type-1 transcription through targeting the transcription factors AP-1 and CREB. Chin Med J (Engl). 2010 Sep;123(17):2440–2445.

Published In

Chin Med J (Engl)

EISSN

2542-5641

Publication Date

September 2010

Volume

123

Issue

17

Start / End Page

2440 / 2445

Location

China

Related Subject Headings

  • U937 Cells
  • Transcription, Genetic
  • Transcription Factor AP-1
  • Tetradecanoylphorbol Acetate
  • Oncology & Carcinogenesis
  • MARVEL Domain-Containing Proteins
  • Jurkat Cells
  • Intracellular Space
  • Humans
  • HIV-1