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 Chen, X.
Right arrow Articles by Force, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, X.
Right arrow Articles by Force, T.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2006, p. 4462-4473, Vol. 26, No. 12
0270-7306/06/$08.00+0     doi:10.1128/MCB.02157-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The ß-Catenin/T-Cell Factor/Lymphocyte Enhancer Factor Signaling Pathway Is Required for Normal and Stress-Induced Cardiac Hypertrophy

Xin Chen,1,{dagger} Sergei P. Shevtsov,2,{dagger} Eileen Hsich,1 Lei Cui,3 Syed Haq,1 Mark Aronovitz,1 Risto Kerkelä,2 Jeffery D. Molkentin,4 Ronglih Liao,3 Robert N. Salomon,5 Richard Patten,1 and Thomas Force1,2*

Molecular Cardiology Research Institute, Tufts-New England Medical Center and Tufts University School of Medicine,1 Department of Pathology, Tufts-New England Medical Center,5 Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts,3 Center for Translational Medicine, Jefferson Medical College, Philadelphia, Pennsylvania,2 Department of Pediatrics, Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio4

Received 7 November 2005/ Returned for modification 6 December 2005/ Accepted 21 March 2006

In cells capable of entering the cell cycle, including cancer cells, ß-catenin has been termed a master switch, driving proliferation over differentiation. However, its role as a transcriptional activator in terminally differentiated cells is relatively unknown. Herein we utilize conditional, cardiac-specific deletion of the ß-catenin gene and cardiac-specific expression of a dominant inhibitory mutant of Lef-1 (Lef-1{Delta}20), one of the members of the T-cell factor/lymphocyte enhancer factor (Tcf/Lef) family of transcription factors that functions as a coactivator with ß-catenin, to demonstrate that ß-catenin/Tcf/Lef-dependent gene expression regulates both physiologic and pathological growth (hypertrophy) of the heart. Indeed, the profound nature of the growth impairment of the heart in the Lef-1{Delta}20 mouse, which leads to very early development of heart failure and premature death, suggests ß-catenin/Tcf/Lef targets are dominant regulators of cardiomyocyte growth. Thus, our studies, employing complementary models in vivo, implicate ß-catenin/Tcf/Lef signaling as an essential growth-regulatory pathway in terminally differentiated cells.

* Corresponding author. Mailing address: Center for Translational Medicine, Jefferson Medical College, 1025 Walnut St., Suite 316, Philadelphia, PA 19107. Phone: (215) 503-9520. Fax: (215) 503-5731. E-mail: thomas.force{at}jefferson.edu.

{dagger} These authors contributed equally.

Molecular and Cellular Biology, June 2006, p. 4462-4473, Vol. 26, No. 12
0270-7306/06/$08.00+0     doi:10.1128/MCB.02157-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Donaldson, C., Eder, S., Baker, C., Aronovitz, M. J., Weiss, A. D., Hall-Porter, M., Wang, F., Ackerman, A., Karas, R. H., Molkentin, J. D., Patten, R. D. (2009). Estrogen Attenuates Left Ventricular and Cardiomyocyte Hypertrophy by an Estrogen Receptor-Dependent Pathway That Increases Calcineurin Degradation. Circ. Res. 104: 265-275 [Abstract] [Full Text]  
  • Grigoryan, T., Wend, P., Klaus, A., Birchmeier, W. (2008). Deciphering the function of canonical Wnt signals in development and disease: conditional loss- and gain-of-function mutations of {beta}-catenin in mice. Genes Dev. 22: 2308-2341 [Abstract] [Full Text]  
  • Cohen, E. D., Tian, Y., Morrisey, E. E. (2008). Wnt signaling: an essential regulator of cardiovascular differentiation, morphogenesis and progenitor self-renewal. Development 135: 789-798 [Abstract] [Full Text]  
  • Hirotani, S., Zhai, P., Tomita, H., Galeotti, J., Marquez, J. P., Gao, S., Hong, C., Yatani, A., Avila, J., Sadoshima, J. (2007). Inhibition of Glycogen Synthase Kinase 3{beta} During Heart Failure Is Protective. Circ. Res. 101: 1164-1174 [Abstract] [Full Text]  
  • Force, T., Woulfe, K., Koch, W. J., Kerkela, R. (2007). Molecular Scaffolds Regulate Bidirectional Crosstalk Between Wnt and Classical Seven-Transmembrane Domain Receptor Signaling Pathways. Sci Signal 2007: pe41-pe41 [Abstract] [Full Text]  
  • Hannigan, G. E., Coles, J. G., Dedhar, S. (2007). Integrin-Linked Kinase at the Heart of Cardiac Contractility, Repair, and Disease. Circ. Res. 100: 1408-1414 [Abstract] [Full Text]  
  • Baurand, A., Zelarayan, L., Betney, R., Gehrke, C., Dunger, S., Noack, C., Busjahn, A., Huelsken, J., Taketo, M. M., Birchmeier, W., Dietz, R., Bergmann, M. W. (2007). {beta}-Catenin Downregulation Is Required for Adaptive Cardiac Remodeling. Circ. Res. 100: 1353-1362 [Abstract] [Full Text]  
  • Ahuja, P., Sdek, P., MacLellan, W. R. (2007). Cardiac Myocyte Cell Cycle Control in Development, Disease, and Regeneration. Physiol. Rev. 87: 521-544 [Abstract] [Full Text]  
  • Zhou, J., Qu, J., Yi, X. P., Graber, K., Huber, L., Wang, X., Gerdes, A. M., Li, F. (2007). Upregulation of {gamma}-catenin compensates for the loss of beta-catenin in adult cardiomyocytes. Am. J. Physiol. Heart Circ. Physiol. 292: H270-H276 [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»