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

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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Polo JM,Dell'Oso T,Ranuncolo SM,Cerchietti L,Beck D,Da Silva GF,Prive GG,Licht JD,Melnick A

doi

10.1038/nm1134

keywords:

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

1329-35

issue

12

eissn

1078-8956

issn

1546-170X

pii

nm1134

journal_volume

10

pub_type

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