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HIC1(hypermethylated in cancer) is a tumour suppressor gene located in 17p13.3, a region frequently hypermethylated or deleted in many types of prevalent human tumour.HIC1is also a candidate for a contiguous-gene syndrome, the Miller–Dieker syndrome, a severe form of lissencephaly accompanied by developmental anomalies. | ềFEBS Journal A L225A substitution in the human tumour suppressor HIC1 abolishes its interaction with the corepressor CtBP Nicolas Stankovic-Valentin1 Alexis Verger2 Sophie Deltour-Balerdi1 Kate G. R. Quinlan2 Merlin Crossley2 and Dominique Lep nce 1 CNRS UMR 8526 Institut de Biologie de Lille Institut Pasteur de Lille France 2 Schoolof Molecular and MicrobialBiosciences University of Sydney New South Wales Australia Keywords 17p13.3 CtBP HIC1 Miller-Dieker syndrome transcriptionalrepression Correspondence D. Leprince CNRS UMR 8161 Institut de Biologie de Lille Institut Pasteur de Lille 1 Rue Calmette 59017 Lille Cedex France Fax 33 3 20 87 1111 Tel 33 3 20 87 1119 E-mail dominique.leprince@ibl.fr Present address CNRS UMR 8161 Institut de Biologie de Lille Institut Pasteur de Lille France tWellcome Trust University of Cambridge UK Received 3 March 2006 revised 27 April 2006 accepted 2 May 2006 doi 10.1111 j.1742-4658.2006.05301.x HIC1 hypermethylated in cancer is a tumour suppressor gene located in 17p13.3 a region frequently hypermethylated or deleted in many types of prevalent human tumour. HIC1 is also a candidate for a contiguous-gene syndrome the Miller-Dieker syndrome a severe form of lissencephaly accompanied by developmental anomalies. HIC1 encodes a BTB POZ-zinc finger transcriptional repressor. HIC1 represses transcription via two autonomous repression domains an N-terminal BTB POZ and a central region by trichostatin A-insensitive and trichostatin A-sensitive mechanisms respectively. The HIC1 central region recruits the corepressor CtBP C-ter-minal binding protein through a conserved GLDLSKK motif a variant of the consensus C-terminal binding protein interaction domain PxDLSxK R. Here we show that HIC1 interacts with both CtBP1 and CtBP2 and that this interaction is stimulated by agents increasing NADH levels. Furthermore point mutation of two CtBP2 residues forming part of the structure of the recognition cleft for a PxDLS motif also ablates the .
