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 Abdellatif, M.
Right arrow Articles by Schneider, M. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Abdellatif, M.
Right arrow Articles by Schneider, M. D.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 1998, p. 6729-6736, Vol. 18, No. 11
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

A Ras-Dependent Pathway Regulates RNA Polymerase II Phosphorylation in Cardiac Myocytes: Implications for Cardiac Hypertrophy

Maha Abdellatif,1,* Sharon E. Packer,1 Lloyd H. Michael,1 Dou Zhang,1 Min Ji Charng,1,dagger and Michael D. Schneider1,2

Molecular Cardiology Unit, Department of Medicine1 and Departments of Cell Biology and Molecular Physiology & Biophysics,2 Baylor College of Medicine, Houston, Texas 77030

Received 23 April 1998/Returned for modification 19 June 1998/Accepted 4 August 1998

Despite extensive evidence implicating Ras in cardiac muscle hypertrophy, the mechanisms involved are unclear. We previously reported that Ras, through an effector-like function of Ras GTPase-activating protein (GAP) in neonatal cardiac myocytes (M. Abdellatif et al., J. Biol. Chem. 269:15423-15426, 1994; M. Abdellatif and M. D. Schneider, J. Biol. Chem. 272:527-533, 1997), can up-regulate expression from a comprehensive set of promoters, including both cardiac cell-specific and constitutive ones. To investigate the mechanism(s) underlying these earlier findings, we have used recombinant adenoviruses harboring a dominant negative Ras (17N Ras) allele or the N-terminal domain of GAP (nGAP), responsible for the Ras-like effector function. Inhibition of endogenous Ras reduced basal levels of [3H]uridine and [3H]phenylalanine incorporation into total RNA, mRNA, and protein, with parallel changes in apparent cell size. In addition, 17N Ras markedly inhibited phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (pol II), known to regulate transcript elongation, accompanied by down-regulation of its principal kinase, cyclin-dependent kinase 7 (Cdk7). In contrast, nGAP elicited the opposite effects on each of these parameters. Furthermore, cotransfection of constitutively active Ras (12R Ras) with wild-type pol II, rather than a truncated mutant lacking the CTD, demonstrated that Ras activation of transcription was dependent on the pol II CTD. Consistent with a potential role for this pathway in the development of cardiac myocyte hypertrophy, alpha 1-adrenergic stimulation similarly enhanced pol II phosphorylation and Cdk7 expression, where both effects were inhibited by dominant negative Ras, while pressure overload hypertrophy led to an increase in both hyperphosphorylated and hypophosphorylated pol II in addition to Cdk7.

* Corresponding author. Mailing address: Department of Medicine, Molecular Cardiology Unit, One Baylor Plaza, Room 506C, Houston, TX 77030. Phone: (713) 798-6912. Fax: (713) 798-7437. E-mail: mahaa{at}bcm.tmc.edu.

dagger Present address: Department of Medicine, Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan.

Molecular and Cellular Biology, November 1998, p. 6729-6736, Vol. 18, No. 11
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Xu, J., Ismat, F. A., Wang, T., Lu, M. M., Antonucci, N., Epstein, J. A. (2009). Cardiomyocyte-Specific Loss of Neurofibromin Promotes Cardiac Hypertrophy and Dysfunction. Circ. Res. 105: 304-311 [Abstract] [Full Text]  
  • Espinoza-Derout, J., Wagner, M., Salciccioli, L., Lazar, J. M., Bhaduri, S., Mascareno, E., Chaqour, B., Siddiqui, M.A.Q. (2009). Positive Transcription Elongation Factor b Activity in Compensatory Myocardial Hypertrophy is Regulated by Cardiac Lineage Protein-1. Circ. Res. 104: 1347-1354 [Abstract] [Full Text]  
  • Sui, X., Li, D., Qiu, H., Gaussin, V., Depre, C. (2009). Activation of the Bone Morphogenetic Protein Receptor by H11Kinase/Hsp22 Promotes Cardiac Cell Growth and Survival. Circ. Res. 104: 887-895 [Abstract] [Full Text]  
  • Guo, W., Wu, S., Wang, L., Wang, R.-y., Wei, X., Liu, J., Fang, B. (2009). Interruption of RNA processing machinery by a small compound, 1-[(4-chlorophenyl)methyl]-1H-indole-3-carboxaldehyde (oncrasin-1). Molecular Cancer Therapeutics 8: 441-448 [Abstract] [Full Text]  
  • Hedhli, N., Wang, L., Wang, Q., Rashed, E., Tian, Y., Sui, X., Madura, K., Depre, C. (2008). Proteasome activation during cardiac hypertrophy by the chaperone H11 Kinase/Hsp22. Cardiovasc Res 77: 497-505 [Abstract] [Full Text]  
  • Sayed, D., Hong, C., Chen, I.-Y., Lypowy, J., Abdellatif, M. (2007). MicroRNAs Play an Essential Role in the Development of Cardiac Hypertrophy. Circ. Res. 100: 416-424 [Abstract] [Full Text]  
  • Chen, I.-Y., Lypowy, J., Pain, J., Sayed, D., Grinberg, S., Alcendor, R. R., Sadoshima, J., Abdellatif, M. (2006). Histone H2A.z Is Essential for Cardiac Myocyte Hypertrophy but Opposed by Silent Information Regulator 2{alpha}. J. Biol. Chem. 281: 19369-19377 [Abstract] [Full Text]  
  • Lypowy, J., Chen, I.-Y., Abdellatif, M. (2005). An Alliance between Ras GTPase-activating Protein, Filamin C, and Ras GTPase-activating Protein SH3 Domain-binding Protein Regulates Myocyte Growth. J. Biol. Chem. 280: 25717-25728 [Abstract] [Full Text]  
  • Sano, M., Schneider, M. D. (2004). Cyclin-Dependent Kinase-9: An RNAPII Kinase at the Nexus of Cardiac Growth and Death Cascades. Circ. Res. 95: 867-876 [Abstract] [Full Text]  
  • Frey, N., Katus, H. A., Olson, E. N., Hill, J. A. (2004). Hypertrophy of the Heart: A New Therapeutic Target?. Circulation 109: 1580-1589 [Abstract] [Full Text]  
  • Yue, Y., Lypowy, J., Hedhli, N., Abdellatif, M. (2004). Ras GTPase-activating Protein Binds to Akt and Is Required for Its Activation. J. Biol. Chem. 279: 12883-12889 [Abstract] [Full Text]  
  • Zheng, M., Dilly, K., Dos Santos Cruz, J., Li, M., Gu, Y., Ursitti, J. A., Chen, J., Ross, J. Jr., Chien, K. R., Lederer, J. W., Wang, Y. (2004). Sarcoplasmic reticulum calcium defect in Ras-induced hypertrophic cardiomyopathy heart. Am. J. Physiol. Heart Circ. Physiol. 286: H424-H433 [Abstract] [Full Text]  
  • GOUNI-BERTHOLD, I., SACHINIDIS, A. (2002). Does the coronary risk factor low density lipoprotein alter growth and signaling in vascular smooth muscle cells?. FASEB J. 16: 1477-1487 [Abstract] [Full Text]  
  • Howard, S. C., Budovskaya, Y. V., Chang, Y.-W., Herman, P. K. (2002). The C-terminal Domain of the Largest Subunit of RNA Polymerase II Is Required for Stationary Phase Entry and Functionally Interacts with the Ras/PKA Signaling Pathway. J. Biol. Chem. 277: 19488-19497 [Abstract] [Full Text]  
  • PETRICH, B.G., LIAO, P., WANG, Y. (2002). Using a Gene-switch Transgenic Approach to Dissect Distinct Roles of MAP Kinases in Heart Failure. Cold Spring Harb Symp Quant Biol 67: 429-438 [Abstract]  
  • Lu, Y., Lian, H., Sharma, P., Schreiber-Agus, N., Russell, R. G., Chin, L., van der Horst, G. T. J., Bregman, D. B. (2001). Disruption of the Cockayne Syndrome B Gene Impairs Spontaneous Tumorigenesis in Cancer-Predisposed Ink4a/ARF Knockout Mice. Mol. Cell. Biol. 21: 1810-1818 [Abstract] [Full Text]  
  • Ho, P. D., Fan, J.-S., Hayes, N. L., Saada, N., Palade, P. T., Glembotski, C. C., McDonough, P. M. (2001). Ras Reduces L-Type Calcium Channel Current in Cardiac Myocytes : Corrective Effects of L-Channels and SERCA2 on [Ca2+]i Regulation and Cell Morphology. Circ. Res. 88: 63-69 [Abstract] [Full Text]  
  • De Windt, L. J., Lim, H. W., Haq, S., Force, T., Molkentin, J. D. (2000). Calcineurin Promotes Protein Kinase C and c-Jun NH2-terminal Kinase Activation in the Heart. CROSS-TALK BETWEEN CARDIAC HYPERTROPHIC SIGNALING PATHWAYS. J. Biol. Chem. 275: 13571-13579 [Abstract] [Full Text]  
  • Bogoyevitch, M. A. (2000). Signalling via stress-activated mitogen-activated protein kinases in the cardiovascular system. Cardiovasc Res 45: 826-842 [Abstract] [Full Text]  
  • Lin, H. H., Zentner, M. D., Ho, H.-L. L., Kim, K.-J., Ann, D. K. (1999). The Gene Expression of the Amiloride-sensitive Epithelial Sodium Channel alpha -Subunit Is Regulated by Antagonistic Effects between Glucocorticoid Hormone and Ras Pathways in Salivary Epithelial Cells. J. Biol. Chem. 274: 21544-21554 [Abstract] [Full Text]  
  • Hines, W. A., Thorburn, J., Thorburn, A. (1999). Cell density and contraction regulate p38 MAP kinasedependent responses in neonatal rat cardiac myocytes. Am. J. Physiol. Heart Circ. Physiol. 277: H331-H341 [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»