This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Qing, J.
Right arrow Articles by Derynck, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Qing, J.
Right arrow Articles by Derynck, R.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2004, p. 1411-1425, Vol. 24, No. 3
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.3.1411-1425.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Transforming Growth Factor ß/Smad3 Signaling Regulates IRF-7 Function and Transcriptional Activation of the Beta Interferon Promoter

Jing Qing,1,{dagger} Cheng Liu,1,{dagger} Lisa Choy,1 Rui-Yun Wu,1 Joseph S. Pagano,2 and Rik Derynck1*

Departments of Growth and Development and Anatomy, Programs in Cell Biology and Developmental Biology, University of California at San Francisco, San Francisco, California,1 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina2

Received 26 June 2002/ Returned for modification 16 August 2002/ Accepted 4 November 2003

The rapid induction of alpha interferon (IFN-{alpha}) and IFN-ß expression plays a critical role in the innate immune response against viral infection. We studied the effects of transforming growth factor ß (TGF-ß) and its intracellular effectors, the Smads, on the function of IRF-7, an essential transcription factor for IFN-{alpha} and -ß induction. IRF-7 interacted with Smads, and IRF-7, but not IRF-3, cooperated with Smad3 to activate IFN-ß transcription. This transcriptional cooperation occurred at the IRF-binding sequences in the IFN-ß promoter, and dominant-negative interference with TGF-ß receptor signaling and Smad3 function decreased IRF-7-mediated transcription. Furthermore, elimination of Smad3 expression in Smad3-/- fibroblasts delayed and decreased double-stranded RNA-induced expression of endogenous IFN-ß, whereas restoration of Smad3 expression enhanced IFN-ß induction. The IRF-7-Smad3 cooperativity resulted from the regulation of the transactivation activity of IRF-7 by Smad3, and dominant-negative interference with Smad3 function decreased IRF-7 activity. Consistent with the regulation by Smad3, the transcriptional activity of IRF-7 depended on and was regulated by TGF-ß signaling. Our studies underscore a role of TGF-ß/Smad3 signaling in IRF-7-mediated induction of IFN-ß expression.

* Corresponding author. Mailing address: Department of Growth and Development, University of California at San Francisco, San Francisco, CA 94143-0640. Phone: (415) 476-7322. Fax: (415) 476-1499. E-mail: derynck{at}itsa.ucsf.edu.

{dagger} J.Q. and C.L. contributed equally to this work.

Molecular and Cellular Biology, February 2004, p. 1411-1425, Vol. 24, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.3.1411-1425.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lin, D.-W., Chang, I.-C., Tseng, A., Wu, M.-L., Chen, C.-H., Patenaude, C. A., Layne, M. D., Yet, S.-F. (2008). Transforming Growth Factor {beta} Up-regulates Cysteine-rich Protein 2 in Vascular Smooth Muscle Cells via Activating Transcription Factor 2. J. Biol. Chem. 283: 15003-15014 [Abstract] [Full Text]  
  • Randall, R. E., Goodbourn, S. (2008). Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J. Gen. Virol. 89: 1-47 [Abstract] [Full Text]  
  • Honda, K., Yanai, H., Takaoka, A., Taniguchi, T. (2005). Regulation of the type I IFN induction: a current view. Int Immunol 17: 1367-1378 [Abstract] [Full Text]  
  • Ning, S., Huye, L. E., Pagano, J. S. (2005). Regulation of the Transcriptional Activity of the IRF7 Promoter by a Pathway Independent of Interferon Signaling. J. Biol. Chem. 280: 12262-12270 [Abstract] [Full Text]  
  • Zhang, L., Zhang, J., Lambert, Q., Der, C. J., Del Valle, L., Miklossy, J., Khalili, K., Zhou, Y., Pagano, J. S. (2004). Interferon Regulatory Factor 7 Is Associated with Epstein-Barr Virus-Transformed Central Nervous System Lymphoma and Has Oncogenic Properties. J. Virol. 78: 12987-12995 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»