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

Authors

  • P. Dhordain
  • O. Albagli
  • R.J. Lin
  • S. Ansieau
  • S. Quief
  • A. Leutz
  • J.P. Kerckaert
  • R.M. Evans
  • D. Leprince

Journal

  • Proceedings of the National Academy of Sciences of the United States of America

Citation

  • Proc Natl Acad Sci U S A 94 (20): 10762-10767

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.


DOI

doi:content/94/20/10762.abstract