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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.



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