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 Deltour, S.
Right arrow Articles by Leprince, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Deltour, S.
Right arrow Articles by Leprince, D.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2002, p. 4890-4901, Vol. 22, No. 13
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.13.4890-4901.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Human Candidate Tumor Suppressor Gene HIC1 Recruits CtBP through a Degenerate GLDLSKK Motif

Sophie Deltour,1 Sébastien Pinte,1 Cateline Guerardel,1 Bohdan Wasylyk,2 and Dominique Leprince1*

CNRS UMR 8526, Institut de Biologie de Lille, Institut Pasteur de Lille, 59017 Lille Cedex,1 IGBMC, CNRS/INSERM/ULP, 67404 Illkirch, France2

Received 4 October 2001/ Returned for modification 21 November 2001/ Accepted 28 March 2002

HIC1 (hypermethylated in cancer) and its close relative HRG22 (HIC1-related gene on chromosome 22) encode transcriptional repressors with five C2H2 zinc fingers and an N-terminal BTB/POZ autonomous transcriptional repression domain that is unable to recruit histone deacetylases (HDACs). Alignment of the HIC1 and HRG22 proteins from various species highlighted a perfectly conserved GLDLSKK/R motif highly related to the consensus CtBP interaction motif (PXDLSXK/R), except for the replacement of the virtually invariant proline by a glycine. HIC1 strongly interacts with mCtBP1 both in vivo and in vitro through this conserved GLDLSKK motif, thus extending the CtBP consensus binding site. The BTB/POZ domain does not interact with mCtBP1, but the dimerization of HIC1 through this domain is required for the interaction with mCtBP1. When tethered to DNA by fusion with the Gal4 DNA-binding domain, the HIC1 central region represses transcription through interactions with CtBP in a trichostatin A-sensitive manner. In conclusion, our results demonstrate that HIC1 mediates transcriptional repression by both HDAC-independent and HDAC-dependent mechanisms and show that CtBP is a HIC1 corepressor that is recruited via a variant binding site.

* Corresponding author. Mailing address: CNRS UMR 8526, Institut de Biologie de Lille, Institut Pasteur de Lille, 1 Rue Calmette, 59017 Lille Cedex, France. Phone: 33 3 20 87 1119. Fax: 33 3 20 87 1111. E-mail: Dominique.Leprince{at} ibl.fr.

Molecular and Cellular Biology, July 2002, p. 4890-4901, Vol. 22, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.13.4890-4901.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Van Rechem, C., Rood, B. R., Touka, M., Pinte, S., Jenal, M., Guerardel, C., Ramsey, K., Monte, D., Begue, A., Tschan, M. P., Stephan, D. A., Leprince, D. (2009). Scavenger Chemokine (CXC Motif) Receptor 7 (CXCR7) Is a Direct Target Gene of HIC1 (Hypermethylated in Cancer 1). J. Biol. Chem. 284: 20927-20935 [Abstract] [Full Text]  
  • Mendez, L. M., Polo, J. M., Yu, J. J., Krupski, M., Ding, B. B., Melnick, A., Ye, B. H. (2008). CtBP Is an Essential Corepressor for BCL6 Autoregulation. Mol. Cell. Biol. 28: 2175-2186 [Abstract] [Full Text]  
  • Briggs, K. J., Corcoran-Schwartz, I. M., Zhang, W., Harcke, T., Devereux, W. L., Baylin, S. B., Eberhart, C. G., Watkins, D. N. (2008). Cooperation between the Hic1 and Ptch1 tumor suppressors in medulloblastoma. Genes Dev. 22: 770-785 [Abstract] [Full Text]  
  • Stankovic-Valentin, N., Deltour, S., Seeler, J., Pinte, S., Vergoten, G., Guerardel, C., Dejean, A., Leprince, D. (2007). An Acetylation/Deacetylation-SUMOylation Switch through a Phylogenetically Conserved {psi}KXEP Motif in the Tumor Suppressor HIC1 Regulates Transcriptional Repression Activity. Mol. Cell. Biol. 27: 2661-2675 [Abstract] [Full Text]  
  • Zhang, Q., Wang, S.-Y., Fleuriel, C., Leprince, D., Rocheleau, J. V., Piston, D. W., Goodman, R. H. (2007). Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex. Proc. Natl. Acad. Sci. USA 104: 829-833 [Abstract] [Full Text]  
  • Quinlan, K. G. R., Verger, A., Kwok, A., Lee, S. H. Y., Perdomo, J., Nardini, M., Bolognesi, M., Crossley, M. (2006). Role of the C-Terminal Binding Protein PXDLS Motif Binding Cleft in Protein Interactions and Transcriptional Repression. Mol. Cell. Biol. 26: 8202-8213 [Abstract] [Full Text]  
  • Verger, A., Quinlan, K. G. R., Crofts, L. A., Spano, S., Corda, D., Kable, E. P. W., Braet, F., Crossley, M. (2006). Mechanisms Directing the Nuclear Localization of the CtBP Family Proteins.. Mol. Cell. Biol. 26: 4882-4894 [Abstract] [Full Text]  
  • Kim, S.-C., Kim, Y.-S., Jetten, A. M. (2005). Kruppel-like zinc finger protein Gli-similar 2 (Glis2) represses transcription through interaction with C-terminal binding protein 1 (CtBP1). Nucleic Acids Res 33: 6805-6815 [Abstract] [Full Text]  
  • Sasai, N., Matsuda, E., Sarashina, E., Ishida, Y., Kawaichi, M. (2005). Identification of a novel BTB-zinc finger transcriptional repressor, CIBZ, that interacts with CtBP corepressor. GENES CELLS 10: 871-885 [Abstract] [Full Text]  
  • Soubry, A., van Hengel, J., Parthoens, E., Colpaert, C., Van Marck, E., Waltregny, D., Reynolds, A. B., van Roy, F. (2005). Expression and Nuclear Location of the Transcriptional Repressor Kaiso Is Regulated by the Tumor Microenvironment. Cancer Res. 65: 2224-2233 [Abstract] [Full Text]  
  • Pinte, S., Stankovic-Valentin, N., Deltour, S., Rood, B. R., Guerardel, C., Leprince, D. (2004). The Tumor Suppressor Gene HIC1 (Hypermethylated in Cancer 1) Is a Sequence-specific Transcriptional Repressor: DEFINITION OF ITS CONSENSUS BINDING SEQUENCE AND ANALYSIS OF ITS DNA BINDING AND REPRESSIVE PROPERTIES. J. Biol. Chem. 279: 38313-38324 [Abstract] [Full Text]  
  • Rodova, M., Kelly, K. F., VanSaun, M., Daniel, J. M., Werle, M. J. (2004). Regulation of the Rapsyn Promoter by Kaiso and {delta}-Catenin. Mol. Cell. Biol. 24: 7188-7196 [Abstract] [Full Text]  
  • Lindsey, J. C., Lusher, M. E., Anderton, J. A., Bailey, S., Gilbertson, R. J., Pearson, A. D.J., Ellison, D. W., Clifford, S. C. (2004). Identification of tumour-specific epigenetic events in medulloblastoma development by hypermethylation profiling. Carcinogenesis 25: 661-668 [Abstract] [Full Text]  
  • Christian, M., Tullet, J. M. A., Parker, M. G. (2004). Characterization of Four Autonomous Repression Domains in the Corepressor Receptor Interacting Protein 140. J. Biol. Chem. 279: 15645-15651 [Abstract] [Full Text]  
  • William, C. M., Tanabe, Y., Jessell, T. M. (2003). Regulation of motor neuron subtype identity by repressor activity of Mnx class homeodomain proteins. Development 130: 1523-1536 [Abstract] [Full Text]  
  • Hickabottom, M., Parker, G. A., Freemont, P., Crook, T., Allday, M. J. (2002). Two Nonconsensus Sites in the Epstein-Barr Virus Oncoprotein EBNA3A Cooperate to Bind the Co-repressor Carboxyl-terminal-binding Protein (CtBP). J. Biol. Chem. 277: 47197-47204 [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»