TitleSpecific peptide interference reveals BCL6 transcriptional and oncogenic mechanisms in B-cell lymphoma cells.
Publication TypeJournal Article
Year of Publication2004
AuthorsPolo, Jose M., Dell'Oso Tania, Ranuncolo Stella Maris, Cerchietti Leandro, Beck David, Da Silva Gustavo F., Prive Gilbert G., Licht Jonathan D., and Melnick Ari
JournalNat Med
Date Published2004 Dec
KeywordsAmino Acid Motifs, B-Lymphocytes, Blotting, Western, DNA-Binding Proteins, Fluorescent Antibody Technique, Gene Expression Regulation, Neoplastic, Genes, Regulator, Humans, Immunoprecipitation, Lymphoma, Large B-Cell, Diffuse, Mutation, Nuclear Proteins, Nuclear Receptor Co-Repressor 1, Nuclear Receptor Co-Repressor 2, Peptides, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-6, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured

<p>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.</p>

Alternate JournalNat Med
PubMed ID15531890
Grant ListCA59936 / CA / NCI NIH HHS / United States
CA99982 / CA / NCI NIH HHS / United States