Open AccessCorepressor SMRT binds the BTB/POZ repressing domain of the LAZ3/BCL6 oncoprotein
Author(s) -
Philippe Dhordain,
Olivier Albagli,
Richard J. Lin,
Stéphane Ansieau,
Sabine Quief,
Achim Leutz,
Jean–Pierre Kerckaert,
Ronald M. Evans,
Dominique Leprince
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.20.10762
Subject(s) - corepressor , biology , nuclear receptor , dna binding domain , thyroid hormone receptor , nuclear receptor co repressor 1 , microbiology and biotechnology , repressor , zinc finger , transcription factor , genetics , gene
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.