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 Nguyen, M. M.
Right arrow Articles by Griep, A. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nguyen, M. M.
Right arrow Articles by Griep, A. E.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2003, p. 8970-8981, Vol. 23, No. 24
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.24.8970-8981.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Requirement of PDZ-Containing Proteins for Cell Cycle Regulation and Differentiation in the Mouse Lens Epithelium

Minh M. Nguyen,1 Marie L. Nguyen,2 Georgina Caruana,3 Alan Bernstein,4 Paul F. Lambert,2 and Anne E. Griep1*

Department of Anatomy,1 McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin,2 Department of Anatomy and Cell Biology, Monash University, Clayton, Victoria, Australia,3 Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, and Canadian Institutes of Health Research, Ottawa, Ontario K1A 0W9, Canada4

Received 10 March 2003/ Returned for modification 17 June 2003/ Accepted 22 September 2003

The roles of PDZ domain-containing proteins such as Dlg and Scrib have been well described for Drosophila; however, their requirement for mammalian development is poorly understood. Here we show that Dlg, Scrib, MAGI1, MAGI3, and MPDZ are expressed in the mouse ocular lens. We demonstrate that the increase in proliferation and defects in cellular adhesion and differentiation observed in epithelia of lenses that express E6, a viral oncoprotein that can bind to several PDZ proteins, including the human homologs of Dlg and Scrib, is dependent on E6's ability to bind these proteins via their PDZ domains. Analyses of lenses from mice carrying an insertional mutation in Dlg (dlggt) show increased proliferation and proliferation in spatially inappropriate regions of the lens, a phenotype similar to that of lenses expressing E6. The results from this study indicate that multiple PDZ domain-containing proteins, including Dlg and Scrib, may be required for maintaining the normal pattern of growth and differentiation in the lens. Furthermore, the phenotypic similarities among the Drosophila dlg mutant, the lenses of dlggt mice, and the lenses of E6 transgenic mice suggest that Dlg may have a conserved function in regulating epithelial cell growth and differentiation across species.

* Corresponding author. Mailing address: Department of Anatomy, University of Wisconsin Medical School, 1300 University Ave., Madison, WI 53706. Phone: (608) 262-8988. Fax: (608) 262-7306. E-mail: aegriep{at}facstaff.wisc.edu.

Molecular and Cellular Biology, December 2003, p. 8970-8981, Vol. 23, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.24.8970-8981.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Rao, P. V., Maddala, R. (2009). Abundant Expression of Ponsin, a Focal Adhesion Protein, in Lens and Downregulation of Its Expression by Impaired Cytoskeletal Signaling. IOVS 50: 1769-1777 [Abstract] [Full Text]  
  • Narayan, N., Massimi, P., Banks, L. (2009). CDK phosphorylation of the discs large tumour suppressor controls its localisation and stability. J. Cell Sci. 122: 65-74 [Abstract] [Full Text]  
  • Garcia-Mata, R., Dubash, A. D., Sharek, L., Carr, H. S., Frost, J. A., Burridge, K. (2007). The Nuclear RhoA Exchange Factor Net1 Interacts with Proteins of the Dlg Family, Affects Their Localization, and Influences Their Tumor Suppressor Activity. Mol. Cell. Biol. 27: 8683-8697 [Abstract] [Full Text]  
  • Arpin-Andre, C., Mesnard, J.-M. (2007). The PDZ Domain-binding Motif of the Human T Cell Leukemia Virus Type 1 Tax Protein Induces Mislocalization of the Tumor Suppressor hScrib in T cells. J. Biol. Chem. 282: 33132-33141 [Abstract] [Full Text]  
  • Storrs, C. H., Silverstein, S. J. (2007). PATJ, a Tight Junction-Associated PDZ Protein, Is a Novel Degradation Target of High-Risk Human Papillomavirus E6 and the Alternatively Spliced Isoform 18 E6. J. Virol. 81: 4080-4090 [Abstract] [Full Text]  
  • Bohl, J., Brimer, N., Lyons, C., Vande Pol, S. B. (2007). The Stardust Family Protein MPP7 Forms a Tripartite Complex with LIN7 and DLG1 That Regulates the Stability and Localization of DLG1 to Cell Junctions. J. Biol. Chem. 282: 9392-9400 [Abstract] [Full Text]  
  • Jing, M., Bohl, J., Brimer, N., Kinter, M., Vande Pol, S. B. (2007). Degradation of Tyrosine Phosphatase PTPN3 (PTPH1) by Association with Oncogenic Human Papillomavirus E6 Proteins. J. Virol. 81: 2231-2239 [Abstract] [Full Text]  
  • Shai, A., Brake, T., Somoza, C., Lambert, P. F. (2007). The Human Papillomavirus E6 Oncogene Dysregulates the Cell Cycle and Contributes to Cervical Carcinogenesis through Two Independent Activities. Cancer Res. 67: 1626-1635 [Abstract] [Full Text]  
  • Mahoney, Z. X., Sammut, B., Xavier, R. J., Cunningham, J., Go, G., Brim, K. L., Stappenbeck, T. S., Miner, J. H., Swat, W. (2006). Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter. Proc. Natl. Acad. Sci. USA 103: 19872-19877 [Abstract] [Full Text]  
  • Zhou, M., Leiberman, J., Xu, J., Lavker, R. M. (2006). A hierarchy of proliferative cells exists in mouse lens epithelium: implications for lens maintenance.. IOVS 47: 2997-3003 [Abstract] [Full Text]  
  • Simonson, S. J.S., Difilippantonio, M. J., Lambert, P. F. (2005). Two Distinct Activities Contribute to Human Papillomavirus 16 E6's Oncogenic Potential. Cancer Res. 65: 8266-8273 [Abstract] [Full Text]  
  • Latorre, I. J., Roh, M. H., Frese, K. K., Weiss, R. S., Margolis, B., Javier, R. T. (2005). Viral oncoprotein-induced mislocalization of select PDZ proteins disrupts tight junctions and causes polarity defects in epithelial cells. J. Cell Sci. 118: 4283-4293 [Abstract] [Full Text]  
  • Lee, C., Laimins, L. A. (2004). Role of the PDZ Domain-Binding Motif of the Oncoprotein E6 in the Pathogenesis of Human Papillomavirus Type 31. J. Virol. 78: 12366-12377 [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»