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Biotech / Medical : Ligand (LGND) Breakout!
LGND 201.29+0.2%Nov 17 3:59 PM EST

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To: Flagrante Delictu who wrote (15308)2/19/1998 10:59:00 AM
From: Henry Niman  Read Replies (1) of 32384
 
Here's a Ron Evans' paper showing the same components in non-Hodgkins lymphomas:

Proc Natl Acad Sci U S A 1997 Sep 30;94(20):10762-10767

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

Dhordain P, Albagli O, Lin RJ, Ansieau S, Quief S, Leutz A, Kerckaert JP, Evans RM,
Leprince D

U124 Institut National de la Sante et de la Recherche Medicale, Institut de Recherches sur le
Cancer de Lille Place de Verdun, F-59045 Lille Cedex France. dhordain@infobiogen.fr

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-a-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.

PMID: 9380707, UI: 98021441
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