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

• DOI: 10.1073/pnas.94.20.10762
• Publication Date: 2002-07-26T14:31:44Z
• Authors: Philippe Dhordain; Olivier Albagli; Richard J. Lin; Stéphane Ansieau; Sabine Quief; Achim Leutz; Jean-Pierre Kerck...; Ronald M. Evans; Dominique Leprince
• Keywords: 0301 basic medicine; Transcription, Genetic; 3. Good health; DNA-Binding Proteins; Repressor Proteins; Mice; 03 medical and health sciences; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-6; Animals; Nuclear Receptor Co-Repressor 2; Cells, Cultured; Protein Binding; Transcription Factors

TheLAZ3/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 SMRTin vitro. Furthermore, DNA-bound LAZ3/BCL6 recruits SMRTin 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.