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Corepressor SMRT binds the BTB/POZ repressing domain of the LAZ3/BCL6 oncoprotein

Item Type:Article
Title:Corepressor SMRT binds the BTB/POZ repressing domain of the LAZ3/BCL6 oncoprotein
Creators Name:Dhordain, P. and Albagli, O. and Lin, R.J. and Ansieau, S. and Quief, S. and Leutz, A. and Kerckaert, J.P. and Evans, R.M. and Leprince, D.
Abstract:The LAZ3/BCL6 (lymphoma-associated zinc finger 3/B cell lymphomas 6) gene frequently is altered in non-Hodgkin lymphomas. It encodes a sequence-specific DNA binding transcriptional repressor that contains a conserved N-terminal domain, termed BTB/POZ (bric-à-brac tramtrack broad complex/pox viruses and zinc fingers). Using a yeast two-hybrid screen, we show here that the LAZ3/BCL6 BTB/POZ domain interacts with the SMRT (silencing mediator of retinoid and thyroid receptor) protein. SMRT originally was identified as a corepressor of unliganded retinoic acid and thyroid receptors and forms a repressive complex with a mammalian homolog of the yeast transcriptional repressor SIN3 and the HDAC-1 histone deacetylase. Protein binding assays demonstrate that the LAZ3/BCL6 BTB/POZ domain directly interacts with SMRT in vitro. Furthermore, DNA-bound LAZ3/BCL6 recruits SMRT in vivo, and both overexpressed proteins completely colocalize in nuclear dots. Finally, overexpression of SMRT enhances the LAZ3/BCL6-mediated repression. These results define SMRT as a corepressor of LAZ3/BCL6 and suggest that LAZ3/BCL6 and nuclear hormone receptors repress transcription through shared mechanisms involving SMRT recruitment and histone deacetylation.
Keywords:Transcriptional Repression, Diffuse Large Cell Lymphomas, Yeast Two-Hybrid Screen, Animals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
Page Range:10762-10767
Date:30 September 1997
Official Publication:http://www.pnas.org/content/94/20/10762.abstract
PubMed:View item in PubMed

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