MCB Try AEM online
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
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 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 Kawai-Kowase, K.
Right arrow Articles by Owens, G. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kawai-Kowase, K.
Right arrow Articles by Owens, G. K.
Molecular and Cellular Biology, September 2005, p. 8009-8023, Vol. 25, No. 18
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.18.8009-8023.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

PIAS1 Activates the Expression of Smooth Muscle Cell Differentiation Marker Genes by Interacting with Serum Response Factor and Class I Basic Helix-Loop-Helix Proteins

Keiko Kawai-Kowase, Meena S. Kumar, Mark H. Hoofnagle, Tadashi Yoshida, and Gary K. Owens*

Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia 22908

Received 2 February 2005/ Returned for modification 8 March 2005/ Accepted 30 June 2005

Although a critical component of vascular disease is modulation of the differentiated state of vascular smooth muscle cells (SMC), the mechanisms governing SMC differentiation are relatively poorly understood. We have previously shown that E-boxes and the ubiquitously expressed class I basic helix-loop-helix (bHLH) proteins, including E2-2 and E12, are important in regulation of the SMC differentiation marker gene, the SM {alpha}-actin gene. The aim of the present study was to identify proteins that bind to class I bHLH proteins in SMC and modulate transcriptional regulation of SMC differentiation marker genes. Herein we report that members of the protein inhibitor of activated STAT (PIAS) family interact with class I bHLH factors as well as serum response factor (SRF). PIAS1 interacted with E2-2 and E12 based on yeast two-hybrid screens, mammalian two-hybrid assays, and/or coimmunoprecipitation assays. Overexpression of PIAS1 significantly activated the SM {alpha}-actin promoter and mRNA expression, as well as SM myosin heavy chain and SM22{alpha}, whereas a small interfering RNA for PIAS1 decreased activity of these promoters, as well as endogenous mRNA expression, and SRF binding to SM {alpha}-actin promoter within intact chromatin in cultured SMC. Of significance, PIAS1 bound to SRF and activated SM {alpha}-actin promoter expression in wild-type but not SRF–/– embryonic stem cells. These results provide novel evidence that PIAS1 modulates transcriptional activation of SMC marker genes through cooperative interactions with both SRF and class I bHLH proteins.


* Corresponding author. Mailing address: Department of Molecular Physiology and Biological Physics, University of Virginia, 415 Lane Road, MR5, Room 1220, P.O. Box 801394, Charlottesville, VA 22908. Phone: (434) 924-2652. Fax: (434) 982-0055. E-mail: gko{at}virginia.edu.


Molecular and Cellular Biology, September 2005, p. 8009-8023, Vol. 25, No. 18
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.18.8009-8023.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:




Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2005 by the American Society for Microbiology. All rights reserved.