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 Medjournal_title
Nature medicineauthors
Polo JM,Dell'Oso T,Ranuncolo SM,Cerchietti L,Beck D,Da Silva GF,Prive GG,Licht JD,Melnick Adoi
10.1038/nm1134keywords:
subject
Has Abstractpub_date
2004-12-01 00:00:00pages
1329-35issue
12eissn
1078-8956issn
1546-170Xpii
nm1134journal_volume
10pub_type
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