Specific peptide interference reveals BCL6 transcriptional and oncogenic mechanisms in B-cell lymphoma cells

Jose M. Polo, Tania Dell'Oso, Stella Maris Ranuncolo, Leandro Cerchietti, David Beck, Gustavo F. Da Silva, Gilbert G. Prive, Jonathan D. Licht, Ari Melnick

Research output: Contribution to journalArticleResearchpeer-review

218 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1329-1335
Number of pages7
JournalNature Medicine
Volume10
Issue number12
DOIs
Publication statusPublished - Dec 2004
Externally publishedYes

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