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 Moon, N. S.
Right arrow Articles by Nepveu, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moon, N. S.
Right arrow Articles by Nepveu, A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2001, p. 6332-6345, Vol. 21, No. 18
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.18.6332-6345.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

S Phase-Specific Proteolytic Cleavage Is Required To Activate Stable DNA Binding by the CDP/Cut Homeodomain Protein

Nam Sung Moon,1,2 Peter Premdas,1 Mary Truscott,1 Lam Leduy,1 Ginette Bérubé,1 and Alain Nepveu1,2,3,4,*

Molecular Oncology Group, McGill University Health Center,1 and Departments of Biochemistry,2 Medicine,3 and Oncology,4 McGill University, Montreal, Quebec, Canada H3A 1A1

Received 14 May 2001/Accepted 13 June 2001

The CCAAT displacement protein (CDP), the homologue of the Drosophila melanogaster Cut protein, contains four DNA binding domains that function in pairs. Cooperation between Cut repeat 3 and the Cut homeodomain allows stable DNA binding to the ATCGAT motif, an activity previously shown to be upregulated in S phase. Here we showed that the full-length CDP/Cut protein is incapable of stable DNA binding and that the ATCGAT binding activity present in cells involves a 110-kDa carboxy-terminal peptide of CDP/Cut. A vector expressing CDP/Cut with Myc and hemagglutinin epitope tags at either end generated N- and C-terminal products of 90 and 110 kDa, suggesting that proteolytic cleavage was involved. In vivo pulse/chase labeling experiments confirmed that the 110-kDa protein was derived from the full-length CDP/Cut protein. Proteolytic processing was weak or not detectable in G0 and G1 but increased in populations of cells enriched in S phase, and the appearance of the 110-kDa protein coincided with the increase in ATCGAT DNA binding. Interestingly, the amino-truncated and the full-length CDP/Cut isoforms exhibited different transcriptional properties in a reporter assay. We conclude that proteolytic processing of CDP/Cut at the G1/S transition generates a CDP/Cut isoform with distinct DNA binding and transcriptional activities. These findings, together with the cleavage of the Scc1 protein at mitosis, suggest that site-specific proteolysis may play an important role in the regulation of cell cycle progression.


* Corresponding author. Mailing address: Molecular Oncology Group, McGill University Health Center, 687 Pine Ave. West, Montreal, Quebec H3A 1A1, Canada. Phone: (514) 842-1231 ext. 5842. Fax: (514) 843-1478. E-mail: alain{at}lan1.molonc.mcgill.ca.


Molecular and Cellular Biology, September 2001, p. 6332-6345, Vol. 21, No. 18
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.18.6332-6345.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Kedinger, V., Sansregret, L., Harada, R., Vadnais, C., Cadieux, C., Fathers, K., Park, M., Nepveu, A. (2009). p110 CUX1 Homeodomain Protein Stimulates Cell Migration and Invasion in Part through a Regulatory Cascade Culminating in the Repression of E-cadherin and Occludin. J. Biol. Chem. 284: 27701-27711 [Abstract] [Full Text]  
  • Cadieux, C., Kedinger, V., Yao, L., Vadnais, C., Drossos, M., Paquet, M., Nepveu, A. (2009). Mouse Mammary Tumor Virus p75 and p110 CUX1 Transgenic Mice Develop Mammary Tumors of Various Histologic Types. Cancer Res. 69: 7188-7197 [Abstract] [Full Text]  
  • Seguin, L., Liot, C., Mzali, R., Harada, R., Siret, A., Nepveu, A., Bertoglio, J. (2009). CUX1 and E2F1 Regulate Coordinated Expression of the Mitotic Complex Genes Ect2, MgcRacGAP, and MKLP1 in S Phase. Mol. Cell. Biol. 29: 570-581 [Abstract] [Full Text]  
  • Wilson, B. J., Harada, R., LeDuy, L., Hollenberg, M. D., Nepveu, A. (2009). CUX1 Transcription Factor Is a Downstream Effector of the Proteinase-activated Receptor 2 (PAR2). J. Biol. Chem. 284: 36-45 [Abstract] [Full Text]  
  • Alcalay, N. I., Sharma, M., Vassmer, D., Chapman, B., Paul, B., Zhou, J., Brantley, J. G., Wallace, D. P., Maser, R. L., Vanden Heuvel, G. B. (2008). Acceleration of polycystic kidney disease progression in cpk mice carrying a deletion in the homeodomain protein Cux1. Am. J. Physiol. Renal Physiol. 295: F1725-F1734 [Abstract] [Full Text]  
  • Thomas, V., Samanta, S., Fikrig, E. (2008). Anaplasma phagocytophilum Increases Cathepsin L Activity, Thereby Globally Influencing Neutrophil Function. Infect. Immun. 76: 4905-4912 [Abstract] [Full Text]  
  • 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]  
  • Truscott, M., Harada, R., Vadnais, C., Robert, F., Nepveu, A. (2008). p110 CUX1 Cooperates with E2F Transcription Factors in the Transcriptional Activation of Cell Cycle-Regulated Genes. Mol. Cell. Biol. 28: 3127-3138 [Abstract] [Full Text]  
  • Goulet, B., Markovic, Y., Leduy, L., Nepveu, A. (2008). Proteolytic Processing of Cut Homeobox 1 by Neutrophil Elastase in the MV4;11 Myeloid Leukemia Cell Line. Mol Cancer Res 6: 644-653 [Abstract] [Full Text]  
  • Harada, R., Vadnais, C., Sansregret, L., Leduy, L., Berube, G., Robert, F., Nepveu, A. (2008). Genome-wide location analysis and expression studies reveal a role for p110 CUX1 in the activation of DNA replication genes. Nucleic Acids Res 36: 189-202 [Abstract] [Full Text]  
  • Truscott, M., Denault, J.-B., Goulet, B., Leduy, L., Salvesen, G. S., Nepveu, A. (2007). Carboxyl-terminal Proteolytic Processing of CUX1 by a Caspase Enables Transcriptional Activation in Proliferating Cells. J. Biol. Chem. 282: 30216-30226 [Abstract] [Full Text]  
  • Goulet, B., Sansregret, L., Leduy, L., Bogyo, M., Weber, E., Chauhan, S. S., Nepveu, A. (2007). Increased Expression and Activity of Nuclear Cathepsin L in Cancer Cells Suggests a Novel Mechanism of Cell Transformation. Mol Cancer Res 5: 899-907 [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]  
  • Bulynko, Y. A., Hsing, L. C., Mason, R. W., Tremethick, D. J., Grigoryev, S. A. (2006). Cathepsin L stabilizes the histone modification landscape on the y chromosome and pericentromeric heterochromatin.. Mol. Cell. Biol. 26: 4172-4184 [Abstract] [Full Text]  
  • Sansregret, L., Goulet, B., Harada, R., Wilson, B., Leduy, L., Bertoglio, J., Nepveu, A. (2006). The p110 Isoform of the CDP/Cux Transcription Factor Accelerates Entry into S Phase.. Mol. Cell. Biol. 26: 2441-2455 [Abstract] [Full Text]  
  • Santaguida, M., Nepveu, A. (2005). Differential Regulation of CDP/Cux p110 by Cyclin A/Cdk2 and Cyclin A/Cdk1. J. Biol. Chem. 280: 32712-32721 [Abstract] [Full Text]  
  • Krupp, J. J., Yaich, L. E., Wessells, R. J., Bodmer, R. (2005). Identification of Genetic Loci That Interact With cut During Drosophila Wing-Margin Development. Genetics 170: 1775-1795 [Abstract] [Full Text]  
  • Zimmer, C., Tiveron, M.-C., Bodmer, R., Cremer, H. (2004). Dynamics of Cux2 Expression Suggests that an Early Pool of SVZ Precursors is Fated to Become Upper Cortical Layer Neurons. Cereb Cortex 14: 1408-1420 [Abstract] [Full Text]  
  • Truscott, M., Raynal, L., Wang, Y., Berube, G., Leduy, L., Nepveu, A. (2004). 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. 279: 49787-49794 [Abstract] [Full Text]  
  • Nishio, H., Walsh, M. J. (2004). CCAAT displacement protein/cut homolog recruits G9a histone lysine methyltransferase to repress transcription. Proc. Natl. Acad. Sci. USA 101: 11257-11262 [Abstract] [Full Text]  
  • Schrem, H., Klempnauer, J., Borlak, J. (2004). Liver-Enriched Transcription Factors in Liver Function and Development. Part II: the C/EBPs and D Site-Binding Protein in Cell Cycle Control, Carcinogenesis, Circadian Gene Regulation, Liver Regeneration, Apoptosis, and Liver-Specific Gene Regulation. Pharmacol. Rev. 56: 291-330 [Abstract] [Full Text]  
  • Erturk, E., Ostapchuk, P., Wells, S. I., Yang, J., Gregg, K., Nepveu, A., Dudley, J. P., Hearing, P. (2003). Binding of CCAAT Displacement Protein CDP to Adenovirus Packaging Sequences. J. Virol. 77: 6255-6264 [Abstract] [Full Text]  
  • Truscott, M., Raynal, L., Premdas, P., Goulet, B., Leduy, L., Berube, G., Nepveu, A. (2003). CDP/Cux Stimulates Transcription from the DNA Polymerase {alpha} Gene Promoter. Mol. Cell. Biol. 23: 3013-3028 [Abstract] [Full Text]  
  • Goulet, B., Watson, P., Poirier, M., Leduy, L., Berube, G., Meterissian, S., Jolicoeur, P., Nepveu, A. (2002). Characterization of a Tissue-specific CDP/Cux Isoform, p75, Activated in Breast Tumor Cells. Cancer Res. 62: 6625-6633 [Abstract] [Full Text]  
  • Boudreau, F., Rings, E. H. H. M., Swain, G. P., Sinclair, A. M., Suh, E. R., Silberg, D. G., Scheuermann, R. H., Traber, P. G. (2002). A Novel Colonic Repressor Element Regulates Intestinal Gene Expression by Interacting with Cux/CDP. Mol. Cell. Biol. 22: 5467-5478 [Abstract] [Full Text]  
  • Santaguida, M., Ding, Q., Berube, G., Truscott, M., Whyte, P., Nepveu, A. (2001). Phosphorylation of the CCAAT Displacement Protein (CDP)/Cux Transcription Factor by Cyclin A-Cdk1 Modulates Its DNA Binding Activity in G2. J. Biol. Chem. 276: 45780-45790 [Abstract] [Full Text]