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 Belaguli, N. S.
Right arrow Articles by Schwartz, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Belaguli, N. S.
Right arrow Articles by Schwartz, R. J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 1999, p. 4582-4591, Vol. 19, No. 7
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Dominant Negative Murine Serum Response Factor: Alternative Splicing within the Activation Domain Inhibits Transactivation of Serum Response Factor Binding Targets

Narasimhaswamy S. Belaguli,1 Wei Zhou,1 Thuy-Hanh T. Trinh,1 Mark W. Majesky,1,2 and Robert J. Schwartz1,*

Departments of Cell Biology1 and Pathology,2 Baylor College of Medicine, Houston, Texas 77030

Received 30 December 1998/Returned for modification 3 April 1999/Accepted 9 April 1999

Primary transcripts encoding the MADS box superfamily of proteins, such as MEF2 in animals and ZEMa in plants, are alternatively spliced, producing several isoformic species. We show here that murine serum response factor (SRF) primary RNA transcripts are alternatively spliced at the fifth exon, deleting approximately one-third of the C-terminal activation domain. Among the different muscle types examined, visceral smooth muscles have a very low ratio of SRFDelta 5 to SRF. Increased levels of SRFDelta 5 correlates well with reduced smooth muscle contractile gene activity within the elastic aortic arch, suggesting important biological roles for differential expression of SRFDelta 5 variant relative to wild-type SRF. SRFDelta 5 forms DNA binding-competent homodimers and heterodimers. SRFDelta 5 acts as a naturally occurring dominant negative regulatory mutant that blocks SRF-dependent skeletal alpha -actin, cardiac alpha -actin, smooth alpha -actin, SM22alpha , and SRF promoter-luciferase reporter activities. Expression of SRFDelta 5 interferes with differentiation of myogenic C2C12 cells and the appearance of skeletal alpha -actin and myogenin mRNAs. SRFDelta 5 repressed the serum-induced activity of the c-fos serum response element. SRFDelta 5 fused to the yeast Gal4 DNA binding domain displayed low transcriptional activity, which was complemented by overexpression of the coactivator ATF6. These results indicate that the absence of exon 5 might be bypassed through recruitment of transcription factors that interact with extra-exon 5 regions in the transcriptional activating domain. The novel alternatively spliced isoform of SRF, SRFDelta 5, may play an important regulatory role in modulating SRF-dependent gene expression.

* Corresponding author. Mailing address: Department of Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-6649. Fax: (713) 798-7799. E-mail: schwartz{at}bcm.tmc.edu.

Molecular and Cellular Biology, July 1999, p. 4582-4591, Vol. 19, No. 7
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Sun, Q., Taurin, S., Sethakorn, N., Long, X., Imamura, M., Wang, D.-Z., Zimmer, W. E., Dulin, N. O., Miano, J. M. (2009). Myocardin-dependent Activation of the CArG Box-rich Smooth Muscle {gamma}-Actin Gene: PREFERENTIAL UTILIZATION OF A SINGLE CArG ELEMENT THROUGH FUNCTIONAL ASSOCIATION WITH THE NKX3.1 HOMEODOMAIN PROTEIN. J. Biol. Chem. 284: 32582-32590 [Abstract] [Full Text]  
  • Zhang, A., David, J. J., Subramanian, S. V., Liu, X., Fuerst, M. D., Zhao, X., Leier, C. V., Orosz, C. G., Kelm, R. J. Jr., Strauch, A. R. (2008). Serum response factor neutralizes Pur{alpha}- and Pur{beta}-mediated repression of the fetal vascular smooth muscle {alpha}-actin gene in stressed adult cardiomyocytes. Am. J. Physiol. Cell Physiol. 294: C702-C714 [Abstract] [Full Text]  
  • Badri, K. R., Zhou, Y., Schuger, L. (2008). Embryological Origin of Airway Smooth Muscle. Proc Am Thorac Soc 5: 4-10 [Abstract] [Full Text]  
  • Asanoma, K., Kato, H., Yamaguchi, S., Shin, C. H., Liu, Z.-P., Kato, K., Inoue, T., Miyanari, Y., Yoshikawa, K., Sonoda, K., Fukushima, K., Wake, N. (2007). HOP/NECC1, A Novel Regulator of Mouse Trophoblast Differentiation. J. Biol. Chem. 282: 24065-24074 [Abstract] [Full Text]  
  • Chow, N., Bell, R. D., Deane, R., Streb, J. W., Chen, J., Brooks, A., Van Nostrand, W., Miano, J. M., Zlokovic, B. V. (2007). Serum response factor and myocardin mediate arterial hypercontractility and cerebral blood flow dysregulation in Alzheimer's phenotype. Proc. Natl. Acad. Sci. USA 104: 823-828 [Abstract] [Full Text]  
  • Zhang, S. X., Garcia-Gras, E., Wycuff, D. R., Marriot, S. J., Kadeer, N., Yu, W., Olson, E. N., Garry, D. J., Parmacek, M. S., Schwartz, R. J. (2005). Identification of Direct Serum-response Factor Gene Targets during Me2SO-induced P19 Cardiac Cell Differentiation. J. Biol. Chem. 280: 19115-19126 [Abstract] [Full Text]  
  • Vlahopoulos, S., Zimmer, W. E., Jenster, G., Belaguli, N. S., Balk, S. P., Brinkmann, A. O., Lanz, R. B., Zoumpourlis, V. C., Schwartz, R. J. (2005). Recruitment of the Androgen Receptor via Serum Response Factor Facilitates Expression of a Myogenic Gene. J. Biol. Chem. 280: 7786-7792 [Abstract] [Full Text]  
  • Yoshida, T., Owens, G. K. (2005). Molecular Determinants of Vascular Smooth Muscle Cell Diversity. Circ. Res. 96: 280-291 [Abstract] [Full Text]  
  • Parmacek, M. S. (2004). Myocardin--Not Quite MyoD. Arterioscler. Thromb. Vasc. Bio. 24: 1535-1537 [Full Text]  
  • Kawai-Kowase, K., Sato, H., Oyama, Y., Kanai, H., Sato, M., Doi, H., Kurabayashi, M. (2004). Basic Fibroblast Growth Factor Antagonizes Transforming Growth Factor-{beta}1-Induced Smooth Muscle Gene Expression Through Extracellular Signal-Regulated Kinase 1/2 Signaling Pathway Activation. Arterioscler. Thromb. Vasc. Bio. 24: 1384-1390 [Abstract] [Full Text]  
  • Owens, G. K., Kumar, M. S., Wamhoff, B. R. (2004). Molecular Regulation of Vascular Smooth Muscle Cell Differentiation in Development and Disease. Physiol. Rev. 84: 767-801 [Abstract] [Full Text]  
  • Ferrario, S., Busscher, J., Franken, J., Gerats, T., Vandenbussche, M., Angenent, G. C., Immink, R. G.H. (2004). Ectopic Expression of the Petunia MADS Box Gene UNSHAVEN Accelerates Flowering and Confers Leaf-Like Characteristics to Floral Organs in a Dominant-Negative Manner. Plant Cell 16: 1490-1505 [Abstract] [Full Text]  
  • Yang, Y., Zhe, X., Phan, S. H., Ullenbruch, M., Schuger, L. (2003). Involvement of Serum Response Factor Isoforms in Myofibroblast Differentiation During Bleomycin-Induced Lung Injury. Am. J. Respir. Cell Mol. Bio. 29: 583-590 [Abstract] [Full Text]  
  • Chang, Y.-F., Wei, J., Liu, X., Chen, Y.-H., Layne, M. D., Yet, S.-F. (2003). Identification of a CArG-independent region of the cysteine-rich protein 2 promoter that directs expression in the developing vasculature. Am. J. Physiol. Heart Circ. Physiol. 285: H1675-H1683 [Abstract] [Full Text]  
  • Harding, E. W., Tang, W., Nichols, K. W., Fernandez, D. E., Perry, S. E. (2003). Expression and Maintenance of Embryogenic Potential Is Enhanced through Constitutive Expression of AGAMOUS-Like 15. Plant Physiol. 133: 653-663 [Abstract] [Full Text]  
  • Chang, J., Wei, L., Otani, T., Youker, K. A., Entman, M. L., Schwartz, R. J. (2003). Inhibitory Cardiac Transcription Factor, SRF-N, Is Generated by Caspase 3 Cleavage in Human Heart Failure and Attenuated by Ventricular Unloading. Circulation 108: 407-413 [Abstract] [Full Text]  
  • Davis, F. J., Gupta, M., Camoretti-Mercado, B., Schwartz, R. J., Gupta, M. P. (2003). Calcium/Calmodulin-dependent Protein Kinase Activates Serum Response Factor Transcription Activity by Its Dissociation from Histone Deacetylase, HDAC4: IMPLICATIONS IN CARDIAC MUSCLE GENE REGULATION DURING HYPERTROPHY. J. Biol. Chem. 278: 20047-20058 [Abstract] [Full Text]  
  • Kumar, M. S., Owens, G. K. (2003). Combinatorial Control of Smooth Muscle-Specific Gene Expression. Arterioscler. Thromb. Vasc. Bio. 23: 737-747 [Abstract] [Full Text]  
  • Du, K. L., Ip, H. S., Li, J., Chen, M., Dandre, F., Yu, W., Lu, M. M., Owens, G. K., Parmacek, M. S. (2003). Myocardin Is a Critical Serum Response Factor Cofactor in the Transcriptional Program Regulating Smooth Muscle Cell Differentiation. Mol. Cell. Biol. 23: 2425-2437 [Abstract] [Full Text]  
  • Demayo, F., Minoo, P., Plopper, C. G., Schuger, L., Shannon, J., Torday, J. S. (2002). Mesenchymal-epithelial interactions in lung development and repair: are modeling and remodeling the same process?. Am. J. Physiol. Lung Cell. Mol. Physiol. 283: L510-L517 [Abstract] [Full Text]  
  • Beqaj, S., Jakkaraju, S., Mattingly, R. R., Pan, D., Schuger, L. (2002). High RhoA activity maintains the undifferentiated mesenchymal cell phenotype, whereas RhoA down-regulation by laminin-2 induces smooth muscle myogenesis. JCB 156: 893-903 [Abstract] [Full Text]  
  • Wang, L., Oh, D. Y., Bogerd, J., Choi, H. S., Ahn, R. S., Seong, J. Y., Kwon, H. B. (2001). Inhibitory Activity of Alternative Splice Variants of the Bullfrog GnRH Receptor-3 on Wild-Type Receptor Signaling. Endocrinology 142: 4015-4025 [Abstract] [Full Text]  
  • Belaguli, N. S., Sepulveda, J. L., Nigam, V., Charron, F., Nemer, M., Schwartz, R. J. (2000). Cardiac Tissue Enriched Factors Serum Response Factor and GATA-4 Are Mutual Coregulators. Mol. Cell. Biol. 20: 7550-7558 [Abstract] [Full Text]  
  • Boggon, T. J., Shan, W., Santagata, S., Myers, S. C., Shapiro, L. (1999). Implication of Tubby Proteins as Transcription Factors by Structure-Based Functional Analysis. Science 286: 2119-2125 [Abstract] [Full Text]  
  • Camoretti-Mercado, B., Liu, H.-W., Halayko, A. J., Forsythe, S. M., Kyle, J. W., Li, B., Fu, Y., McConville, J., Kogut, P., Vieira, J. E., Patel, N. M., Hershenson, M. B., Fuchs, E., Sinha, S., Miano, J. M., Parmacek, M. S., Burkhardt, J. K., Solway, J. (2000). Physiological Control of Smooth Muscle-specific Gene Expression through Regulated Nuclear Translocation of Serum Response Factor. J. Biol. Chem. 275: 30387-30393 [Abstract] [Full Text]  
  • Mack, C. P., Somlyo, A. V., Hautmann, M., Somlyo, A. P., Owens, G. K. (2001). Smooth Muscle Differentiation Marker Gene Expression Is Regulated by RhoA-mediated Actin Polymerization. J. Biol. Chem. 276: 341-347 [Abstract] [Full Text]  
  • Carson, J. A., Fillmore, R. A., Schwartz, R. J., Zimmer, W. E. (2000). The Smooth Muscle gamma -Actin Gene Promoter Is a Molecular Target for the Mouse bagpipe Homologue, mNkx3-1, and Serum Response Factor. J. Biol. Chem. 275: 39061-39072 [Abstract] [Full Text]  
  • Gupta, M., Kogut, P., Davis, F. J., Belaguli, N. S., Schwartz, R. J., Gupta, M. P. (2001). Physical Interaction between the MADS Box of Serum Response Factor and the TEA/ATTS DNA-binding Domain of Transcription Enhancer Factor-1. J. Biol. Chem. 276: 10413-10422 [Abstract] [Full Text]  
  • Chang, P. S., Li, L., McAnally, J., Olson, E. N. (2001). Muscle Specificity Encoded by Specific Serum Response Factor-binding Sites. J. Biol. Chem. 276: 17206-17212 [Abstract] [Full Text]  
  • Strobeck, M., Kim, S., Zhang, J. C. L., Clendenin, C., Du, K. L., Parmacek, M. S. (2001). Binding of Serum Response Factor to CArG Box Sequences Is Necessary but Not Sufficient to Restrict Gene Expression to Arterial Smooth Muscle Cells. J. Biol. Chem. 276: 16418-16424 [Abstract] [Full Text]  
  • Drewett, V., Devitt, A., Saxton, J., Portman, N., Greaney, P., Cheong, N., Alnemri, T. F., Alnemri, E., Shaw, P. E. (2001). Serum Response Factor Cleavage by Caspases 3 and 7 Linked to Apoptosis in Human BJAB Cells. J. Biol. Chem. 276: 33444-33451 [Abstract] [Full Text]  
  • Beqaj, S., Jakkaraju, S., Mattingly, R. R., Pan, D., Schuger, L. (2002). High RhoA activity maintains the undifferentiated mesenchymal cell phenotype, whereas RhoA down-regulation by laminin-2 induces smooth muscle myogenesis. JCB 156: 893-903 [Abstract] [Full Text]  
  • Davis, F. J., Gupta, M., Pogwizd, S. M., Bacha, E., Jeevanandam, V., Gupta, M. P. (2002). Increased expression of alternatively spliced dominant-negative isoform of SRF in human failing hearts. Am. J. Physiol. Heart Circ. Physiol. 282: H1521-H1533 [Abstract] [Full Text]  
  • Manabe, I., Owens, G. K. (2001). Recruitment of Serum Response Factor and Hyperacetylation of Histones at Smooth Muscle-Specific Regulatory Regions During Differentiation of a Novel P19-Derived In Vitro Smooth Muscle Differentiation System. Circ. Res. 88: 1127-1134 [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»