Nature Medicine10, 1329 - 1335 (2004)
Published online: 7 November 2004; | doi:10.1038/nm1134
Specific peptide interference reveals BCL6 transcriptional and oncogenic mechanisms in B-cell lymphoma cells
Jose M Polo1, Tania Dell'Oso1, Stella Maris Ranuncolo1, Leandro Cerchietti1, David Beck1, Gustavo F Da Silva1, Gilbert G Prive2, Jonathan D Licht3
& Ari Melnick1
1
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York
10461, USA.
2
Ontario Cancer Institute, University of Toronto, 610 University Avenue, Toronto, Ontario
M5G 2M9, Canada.
3
Department of Medicine, Mount Sinai School of Medicine, One Gustave Levy Place, New York, New York
10029, USA.
The BTB/POZ transcriptional repressor and candidate oncogene BCL6 is frequently misregulated in B-cell lymphomas. The interface through which the BCL6 BTB domain mediates recruitment of the SMRT, NCoR and BCoR corepressors was recently identified. To determine the contribution of this interface to BCL6 transcriptional and biological properties, we generated a peptide that specifically binds BCL6 and blocks corepressor recruitment in vivo. This inhibitor disrupts BCL6-mediated repression and establishment of silenced chromatin, reactivates natural BCL6 target genes, and abrogates BCL6 biological function in B cells. In BCL6-positive lymphoma cells, peptide blockade caused apoptosis and cell cycle arrest. BTB domain peptide inhibitors may constitute a novel therapeutic agent for B-cell lymphomas.
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