Specific peptide interference reveals BCL6 transcriptional and oncogenic mechanisms in B-cell lymphoma cells.
Nat Med
; 10(12): 1329-35, 2004 Dec.
Article
in En
| MEDLINE
| ID: mdl-15531890
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides
/
B-Lymphocytes
/
Gene Expression Regulation, Neoplastic
/
Genes, Regulator
/
Lymphoma, Large B-Cell, Diffuse
/
DNA-Binding Proteins
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Nat Med
Journal subject:
BIOLOGIA MOLECULAR
/
MEDICINA
Year:
2004
Document type:
Article
Affiliation country:
United States