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

Overview

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.

publication date

  • November 7, 2004

Research

keywords

  • B-Lymphocytes
  • DNA-Binding Proteins
  • Gene Expression Regulation, Neoplastic
  • Genes, Regulator
  • Lymphoma, Large B-Cell, Diffuse
  • Peptides

Identity

Scopus Document Identifier

  • 11144277489

Digital Object Identifier (DOI)

  • 10.1038/nm1134

PubMed ID

  • 15531890

Additional Document Info

volume

  • 10

issue

  • 12