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 Zhu, Q.
Right arrow Articles by Dudley, J. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhu, Q.
Right arrow Articles by Dudley, J. P.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2004, p. 4810-4823, Vol. 24, No. 11
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.11.4810-4823.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Homeodomain Protein CDP Regulates Mammary-Specific Gene Transcription and Tumorigenesis

Quan Zhu,1,{dagger} Urmila Maitra,1 Dennis Johnston,2 Mary Lozano,1 and Jaquelin P. Dudley1*

Section of Molecular Genetics and Microbiology and Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712,1 Department of Biomathematics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 770302

Received 22 August 2003/ Returned for modification 3 November 2003/ Accepted 6 March 2004

The CCAAT-displacement protein (CDP) has been implicated in developmental and cell-type-specific regulation of many cellular and viral genes. We previously have shown that CDP represses mouse mammary tumor virus (MMTV) transcription in tissue culture cells. Since CDP-binding activity for the MMTV long terminal repeat declines during mammary development, we tested whether binding mutations could alter viral expression. Infection of mice with MMTV proviruses containing CDP binding site mutations elevated viral RNA levels in virgin mammary glands and shortened mammary tumor latency. To determine if CDP has direct effects on MMTV transcription rather than viral spread, virgin mammary glands of homozygous CDP-mutant mice lacking one of three Cut repeat DNA-binding domains ({Delta}CR1) were examined by reverse transcription-PCR. RNA levels of endogenous MMTV as well as {alpha}-lactalbumin and whey acidic protein (WAP) were elevated. Heterozygous mice with a different CDP mutation that eliminated the entire C terminus and the homeodomain ({Delta}C mice) showed increased levels of MMTV, ß-casein, WAP, and {alpha}-lactalbumin RNA in virgin mammary glands compared to those from wild-type animals. No differences in amounts of WDNM1, {varepsilon}-casein, or glyceraldehyde-3-phosphate dehydrogenase RNA were observed between the undifferentiated mammary tissues from wild-type and mutant mice, indicating the specificity of this effect. These data show independent contributions of different CDP domains to negative regulation of differentiation-specific genes in the mammary gland.

* Corresponding author. Mailing address: Section of Molecular Genetics and Microbiology, The University of Texas at Austin, One University Station, A5000, 24th and Speedway, ESB 226, Austin, TX 78712-0162. Phone: (512) 471-8415. Fax: (512) 471-7088. E-mail: jdudley{at}uts.cc.utexas.edu.

{dagger} Present address: Laboratory of Genetics, The Salk Institute, San Diego, CA 92186-5800.

Molecular and Cellular Biology, June 2004, p. 4810-4823, Vol. 24, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.11.4810-4823.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Cadieux, C., Harada, R., Paquet, M., Cote, O., Trudel, M., Nepveu, A., Bouchard, M. (2008). Polycystic Kidneys Caused by Sustained Expression of Cux1 Isoform p75. J. Biol. Chem. 283: 13817-13824 [Abstract] [Full Text]  
  • Maitra, U., Seo, J., Lozano, M. M., Dudley, J. P. (2006). Differentiation-Induced Cleavage of Cutl1/CDP Generates a Novel Dominant-Negative Isoform That Regulates Mammary Gene Expression. Mol. Cell. Biol. 26: 7466-7478 [Abstract] [Full Text]  
  • Cadieux, C., Fournier, S., Peterson, A. C., Bedard, C., Bedell, B. J., Nepveu, A. (2006). Transgenic Mice Expressing the p75 CCAAT-Displacement Protein/Cut Homeobox Isoform Develop a Myeloproliferative Disease-Like Myeloid Leukemia. Cancer Res. 66: 9492-9501 [Abstract] [Full Text]  
  • Mertz, J. A., Simper, M. S., Lozano, M. M., Payne, S. M., Dudley, J. P. (2005). Mouse Mammary Tumor Virus Encodes a Self-Regulatory RNA Export Protein and Is a Complex Retrovirus. J. Virol. 79: 14737-14747 [Abstract] [Full Text]  
  • Bhadra, S., Lozano, M. M., Dudley, J. P. (2005). Conversion of Mouse Mammary Tumor Virus to a Lymphomagenic Virus. J. Virol. 79: 12592-12596 [Abstract] [Full Text]  
  • Seo, J., Lozano, M. M., Dudley, J. P. (2005). Nuclear Matrix Binding Regulates SATB1-mediated Transcriptional Repression. J. Biol. Chem. 280: 24600-24609 [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»