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

P Dhordain, O Albagli, RJ Lin… - Proceedings of the …, 1997 - National Acad Sciences
P Dhordain, O Albagli, RJ Lin, S Ansieau, S Quief, A Leutz, JP Kerckaert, RM Evans
Proceedings of the National Academy of Sciences, 1997National Acad Sciences
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-ŕ-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 …
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-ŕ-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.
National Acad Sciences