This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goulet, B. Articles by Nepveu, A. Search for Related Content PubMed PubMed Citation Articles by Goulet, B. Articles by Nepveu, A.

Characterization of a Tissue-specific CDP/Cux Isoform, p75, Activated in Breast Tumor Cells¹

Molecular Oncology Group [B. G., M. P., L. L., G. B., A. N.] and Department of Surgical Oncology [M. P., S. M.], McGill University Health Center, Montreal, Quebec, QC H3A 1A1; Departments of Biochemistry [B. G., A. N.], Medicine [A. N.], and Oncology [A. N.], McGill University, Montreal, Quebec, QC H3A 1A1; Department of Pathology & Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, R3E-0W3 [P. W.]; and Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Department of Microbiology and Immunology, Université de Montréal, and Experimental Medicine, McGill University, Montreal, Quebec H2W-1R7 [P. J.], Canada

Two isoforms of the CCAAT-displacement protein/cut homeobox (CDP/Cux) transcription factor have been characterized thus far. The full length protein, p200, which contains four DNA binding domains, transiently binds to DNA and carries the CCAAT-displacement activity. The p110 isoform is generated by proteolytic processing at the G₁-S transition and is capable of stable interaction with DNA. Here we demonstrate the existence of a shorter CDP/Cux isoform, p75, which contains only two DNA binding domains, Cut repeat 3 and the Cut homeodomain, and binds more stably to DNA. CDP/Cux p75 was able to repress a reporter carrying the promoter for the cyclin-dependent kinase inhibitor p21 gene and to activate a DNA polymerase gene reporter. Expression of CDP/Cux p75 involved a novel mechanism: transcription initiation within intron 20. The intron 20-initiated mRNA (I20-mRNA) was expressed at higher level in the thymus and in CD4+/CD8+ and CD4+ T cells. I20-mRNA was expressed only weakly or not at all in normal human mammary epithelial cells and normal breast tissues but was detected in many breast tumor cells lines and breast tumors. In invasive tumors a significant association was established between higher I20-mRNA expression and a diffuse infiltrative growth pattern (n = 41, P = 0.0137). In agreement with these findings, T47D breast cancer cells stably expressing p75 could not form tubule structures in collagen but rather developed as solid undifferentiated aggregates of cells. Taken together, these results suggest that aberrant expression of the CDP/Cux p75 isoform in mammary epithelial cells may be associated with the process of tumorigenesis in breast cancer.

This article has been cited by other articles:

				N. I. Alcalay, M. Sharma, D. Vassmer, B. Chapman, B. Paul, J. Zhou, J. G. Brantley, D. P. Wallace, R. L. Maser, and G. B. Vanden Heuvel Acceleration of polycystic kidney disease progression in cpk mice carrying a deletion in the homeodomain protein Cux1 Am J Physiol Renal Physiol, December 1, 2008; 295(6): F1725 - F1734. [Abstract] [Full Text] [PDF]

				V. Thomas, S. Samanta, and E. Fikrig Anaplasma phagocytophilum Increases Cathepsin L Activity, Thereby Globally Influencing Neutrophil Function Infect. Immun., November 1, 2008; 76(11): 4905 - 4912. [Abstract] [Full Text] [PDF]

				C. Cadieux, R. Harada, M. Paquet, O. Cote, M. Trudel, A. Nepveu, and M. Bouchard Polycystic Kidneys Caused by Sustained Expression of Cux1 Isoform p75 J. Biol. Chem., May 16, 2008; 283(20): 13817 - 13824. [Abstract] [Full Text] [PDF]

				M. Truscott, R. Harada, C. Vadnais, F. Robert, and A. Nepveu p110 CUX1 Cooperates with E2F Transcription Factors in the Transcriptional Activation of Cell Cycle-Regulated Genes Mol. Cell. Biol., May 15, 2008; 28(10): 3127 - 3138. [Abstract] [Full Text] [PDF]

				B. Goulet, Y. Markovic, L. Leduy, and A. Nepveu Proteolytic Processing of Cut Homeobox 1 by Neutrophil Elastase in the MV4;11 Myeloid Leukemia Cell Line Mol. Cancer Res., April 1, 2008; 6(4): 644 - 653. [Abstract] [Full Text] [PDF]

				M. Truscott, J.-B. Denault, B. Goulet, L. Leduy, G. S. Salvesen, and A. Nepveu Carboxyl-terminal Proteolytic Processing of CUX1 by a Caspase Enables Transcriptional Activation in Proliferating Cells J. Biol. Chem., October 12, 2007; 282(41): 30216 - 30226. [Abstract] [Full Text] [PDF]

				B. Goulet, L. Sansregret, L. Leduy, M. Bogyo, E. Weber, S. S. Chauhan, and A. Nepveu Increased Expression and Activity of Nuclear Cathepsin L in Cancer Cells Suggests a Novel Mechanism of Cell Transformation Mol. Cancer Res., September 1, 2007; 5(9): 899 - 907. [Abstract] [Full Text] [PDF]

				U. Maitra, J. Seo, M. M. Lozano, and J. P. Dudley Differentiation-Induced Cleavage of Cutl1/CDP Generates a Novel Dominant-Negative Isoform That Regulates Mammary Gene Expression Mol. Cell. Biol., October 15, 2006; 26(20): 7466 - 7478. [Abstract] [Full Text] [PDF]

				C. Cadieux, S. Fournier, A. C. Peterson, C. Bedard, B. J. Bedell, and A. Nepveu Transgenic Mice Expressing the p75 CCAAT-Displacement Protein/Cut Homeobox Isoform Develop a Myeloproliferative Disease-Like Myeloid Leukemia Cancer Res., October 1, 2006; 66(19): 9492 - 9501. [Abstract] [Full Text] [PDF]

				P. Michl, B. Knobel, and J. Downward CUTL1 Is Phosphorylated by Protein Kinase A, Modulating Its Effects on Cell Proliferation and Motility J. Biol. Chem., June 2, 2006; 281(22): 15138 - 15144. [Abstract] [Full Text] [PDF]

				L. Sansregret, B. Goulet, R. Harada, B. Wilson, L. Leduy, J. Bertoglio, and A. Nepveu The p110 Isoform of the CDP/Cux Transcription Factor Accelerates Entry into S Phase. Mol. Cell. Biol., March 1, 2006; 26(6): 2441 - 2455. [Abstract] [Full Text] [PDF]

				A. L. Gartel and S. K. Radhakrishnan Lost in Transcription: p21 Repression, Mechanisms, and Consequences Cancer Res., May 15, 2005; 65(10): 3980 - 3985. [Abstract] [Full Text] [PDF]

				M. Truscott, L. Raynal, Y. Wang, G. Berube, L. Leduy, and A. Nepveu The N-terminal Region of the CCAAT Displacement Protein (CDP)/Cux Transcription Factor Functions as an Autoinhibitory Domain that Modulates DNA Binding J. Biol. Chem., November 26, 2004; 279(48): 49787 - 49794. [Abstract] [Full Text] [PDF]

				H. Nishio and M. J. Walsh CCAAT displacement protein/cut homolog recruits G9a histone lysine methyltransferase to repress transcription PNAS, August 3, 2004; 101(31): 11257 - 11262. [Abstract] [Full Text] [PDF]

				M. Truscott, L. Raynal, P. Premdas, B. Goulet, L. Leduy, G. Berube, and A. Nepveu CDP/Cux Stimulates Transcription from the DNA Polymerase {alpha} Gene Promoter Mol. Cell. Biol., April 15, 2003; 23(8): 3013 - 3028. [Abstract] [Full Text] [PDF]