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 Oster, S. K.
Right arrow Articles by Penn, L. Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Oster, S. K.
Right arrow Articles by Penn, L. Z.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2000, p. 6768-6778, Vol. 20, No. 18
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Myc Is an Essential Negative Regulator of Platelet-Derived Growth Factor Beta Receptor Expression

Sara K. Oster,1,2 Wilson W. Marhin,2,3 Charlotte Asker,2,dagger Linda M. Facchini,2,3,Dagger Patrick A. Dion,2,§ Keiko Funa,4 Martin Post,5 John M. Sedivy,6 and Linda Z. Penn1,2,3,*

Departments of Medical Biophysics1 and Molecular and Medical Genetics,2 University of Toronto, and Ontario Cancer Institute,3 Toronto, Ontario, Canada M5G 2M9; Department of Pediatrics, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada M5G 1X85; Institute of Anatomy and Cell Biology, Göteborg University, SE-405 30 Gothenburg, Sweden4; and Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 029126

Received 9 May 2000/Accepted 19 June 2000

Platelet-derived growth factor BB (PDGF BB) is a potent mitogen for fibroblasts as well as many other cell types. Interaction of PDGF BB with the PDGF beta  receptor (PDGF-beta R) activates numerous signaling pathways and leads to a decrease in receptor expression on the cell surface. PDGF-beta R downregulation is effected at two levels, the immediate internalization of ligand-receptor complexes and the reduction in pdgf-beta r mRNA expression. Our studies show that pdgf-beta r mRNA suppression is regulated by the c-myc proto-oncogene. Both constitutive and inducible ectopic Myc protein can suppress pdgf-beta r mRNA and protein. Suppression of pdgf-beta r mRNA in response to Myc is specific, since expression of the related receptor pdgf-alpha r is not affected. We further show that Myc suppresses pdgf-beta r mRNA expression by a mechanism which is distinguishable from Myc autosuppression. Analysis of c-Myc-null fibroblasts demonstrates that Myc is required for the repression of pdgf-beta r mRNA expression in quiescent fibroblasts following mitogen stimulation. In addition, it is evident that the Myc-mediated repression of pdgf-beta r mRNA levels plays an important role in the regulation of basal pdgf-beta r expression in proliferating cells. Thus, our studies suggest an essential role for Myc in a negative-feedback loop regulating the expression of the PDGF-beta R.

* Corresponding author. Mailing address: Division of Cellular and Molecular Biology, Department of Medical Biophysics, 610 University Ave., Toronto, Ontario, Canada M5G 2M9. Phone: (416) 946-2276. Fax: (416) 946-2065. E-mail: lpenn{at}oci.utoronto.ca.

dagger Present address: Rodiumhemmet, Karolinska Sjukhuset, S-171 76 Stockholm, Sweden.

Dagger Present address: Department of Microbiology, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada M5G 1X8.

§ Present address: The Montreal General Hospital Institute, Centre for Research in Neurosciences, Montreal, Quebec, Canada H3G 1A4.

Molecular and Cellular Biology, September 2000, p. 6768-6778, Vol. 20, No. 18
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Kim, S. S., Shago, M., Kaustov, L., Boutros, P. C., Clendening, J. W., Sheng, Y., Trentin, G. A., Barsyte-Lovejoy, D., Mao, D. Y.L., Kay, R., Jurisica, I., Arrowsmith, C. H., Penn, L. Z. (2007). CUL7 Is a Novel Antiapoptotic Oncogene. Cancer Res. 67: 9616-9622 [Abstract] [Full Text]  
  • Lechuga, C. G., Hernandez-Nazara, Z. H., Hernandez, E., Bustamante, M., Desierto, G., Cotty, A., Dharker, N., Choe, M., Rojkind, M. (2006). PI3K is involved in PDGF-beta receptor upregulation post-PDGF-BB treatment in mouse HSC. Am. J. Physiol. Gastrointest. Liver Physiol. 291: G1051-G1061 [Abstract] [Full Text]  
  • Brady, G., Boggan, L., Bowie, A., O'Neill, L. A. J. (2005). Schlafen-1 Causes a Cell Cycle Arrest by Inhibiting Induction of Cyclin D1. J. Biol. Chem. 280: 30723-30734 [Abstract] [Full Text]  
  • Stojadinovic, O., Brem, H., Vouthounis, C., Lee, B., Fallon, J., Stallcup, M., Merchant, A., Galiano, R. D., Tomic-Canic, M. (2005). Molecular Pathogenesis of Chronic Wounds: The Role of {beta}-Catenin and c-myc in the Inhibition of Epithelialization and Wound Healing. Am. J. Pathol. 167: 59-69 [Abstract] [Full Text]  
  • Uramoto, H., Wetterskog, D., Hackzell, A., Matsumoto, Y., Funa, K. (2004). p73 competes with co-activators and recruits histone deacetylase to NF-Y in the repression of PDGF {beta}-receptor. J. Cell Sci. 117: 5323-5331 [Abstract] [Full Text]  
  • Uramoto, H., Hackzell, A., Wetterskog, D., Ballagi, A., Izumi, H., Funa, K. (2004). pRb, Myc and p53 are critically involved in SV40 large T antigen repression of PDGF {beta}-receptor transcription. J. Cell Sci. 117: 3855-3865 [Abstract] [Full Text]  
  • Mao, D. Y. L., Barsyte-Lovejoy, D., Ho, C. S. W., Watson, J. D., Stojanova, A., Penn, L. Z. (2004). Promoter-binding and repression of PDGFRB by c-Myc are separable activities. Nucleic Acids Res 32: 3462-3468 [Abstract] [Full Text]  
  • Frye, M., Gardner, C., Li, E. R., Arnold, I., Watt, F. M. (2003). Evidence that Myc activation depletes the epidermal stem cell compartment by modulating adhesive interactions with the local microenvironment. Development 130: 2793-2808 [Abstract] [Full Text]  
  • Sanchez-Carbayo, M., Socci, N. D., Charytonowicz, E., Lu, M., Prystowsky, M., Childs, G., Cordon-Cardo, C. (2002). Molecular Profiling of Bladder Cancer Using cDNA Microarrays: Defining Histogenesis and Biological Phenotypes. Cancer Res. 62: 6973-6980 [Abstract] [Full Text]  
  • Hackzell, A., Uramoto, H., Izumi, H., Kohno, K., Funa, K. (2002). p73 Independent of c-Myc Represses Transcription of Platelet-derived Growth Factor beta -Receptor through Interaction with NF-Y. J. Biol. Chem. 277: 39769-39776 [Abstract] [Full Text]  
  • Watson, J. D., Oster, S. K., Shago, M., Khosravi, F., Penn, L. Z. (2002). Identifying Genes Regulated in a Myc-dependent Manner. J. Biol. Chem. 277: 36921-36930 [Abstract] [Full Text]  
  • Chiarugi, P., Cirri, P., Taddei, M. L., Talini, D., Doria, L., Fiaschi, T., Buricchi, F., Giannoni, E., Camici, G., Raugei, G., Ramponi, G. (2002). New perspectives in PDGF receptor downregulation: the main role of phosphotyrosine phosphatases. J. Cell Sci. 115: 2219-2232 [Abstract] [Full Text]  
  • Soucie, E. L., Annis, M. G., Sedivy, J., Filmus, J., Leber, B., Andrews, D. W., Penn, L. Z. (2001). Myc Potentiates Apoptosis by Stimulating Bax Activity at the Mitochondria. Mol. Cell. Biol. 21: 4725-4736 [Abstract] [Full Text]  
  • Izumi, H, Molander, C, Penn, L., Ishisaki, A, Kohno, K, Funa, K (2001). Mechanism for the transcriptional repression by c-Myc on PDGF (&bgr;)-receptor. J. Cell Sci. 114: 1533-1544 [Abstract]  


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