BCoR, a novel corepressor involved in BCL-6 repression.

in Genes & development by K D Huynh, W Fischle, E Verdin, V J Bardwell

TLDR

  • The study found a new protein called BCoR that can help stop the growth of certain types of cancer cells. This protein can work with another protein called BCL-6 to stop the cancer cells from growing. The study also found that BCoR is important for the growth of cancer cells and could be a potential target for treatment.

Abstract

BCL-6 encodes a POZ/zinc finger transcriptional repressor that is required for germinal center formation and may influence apoptosis. Aberrant expression of BCL-6 due to chromosomal translocations is implicated in certain subtypes of non-Hodgkin's lymphoma. The POZ domains of BCL-6 and several other POZ proteins interact with corepressors N-CoR and SMRT. Here we identify and characterize a novel corepressor BCoR (BCL-6 interacting corepressor), which is expressed ubiquitously in human tissues. BCoR can function as a corepressor when tethered to DNA and, when overexpressed, can potentiate BCL-6 repression. Specific class I and II histone deacetylases (HDACs) interact in vivo with BCoR, suggesting that BCoR may functionally link these two classes of HDACs. Strikingly, BCoR interacts selectively with the POZ domain of BCL-6 but not with eight other POZ proteins tested, including PLZF. Additionally, interactions between the BCL-6 POZ domain and SMRT, N-CoR, and BCoR are mutually exclusive. The specificity of the BCL-6/BCoR interaction suggests that BCoR may have a role in BCL-6-associated lymphomas.

Overview

  • The study focuses on BCL-6, a POZ/zinc finger transcriptional repressor required for germinal center formation and implicated in certain subtypes of non-Hodgkin's lymphoma. The study aims to identify and characterize a novel corepressor BCoR that interacts with BCL-6 and may have a role in BCL-6-associated lymphomas. The methodology used includes identifying BCoR through a yeast two-hybrid screen and characterizing its function through in vitro and in vivo assays. The primary objective of the study is to understand the role of BCoR in BCL-6-associated lymphomas and its potential as a therapeutic target.

Comparative Analysis & Findings

  • The study compares the interaction between BCoR and BCL-6 with the interactions between BCoR and eight other POZ proteins, including PLZF. The results show that BCoR interacts selectively with the POZ domain of BCL-6 but not with the other POZ proteins. Additionally, interactions between the BCL-6 POZ domain and SMRT, N-CoR, and BCoR are mutually exclusive. These findings suggest that BCoR may have a unique role in BCL-6-associated lymphomas.

Implications and Future Directions

  • The study's findings suggest that BCoR may have a role in BCL-6-associated lymphomas and could be a potential therapeutic target. However, the study has limitations, such as the need for further validation of the BCoR/BCL-6 interaction in vivo. Future research directions could include investigating the role of BCoR in BCL-6-associated lymphomas and its potential as a therapeutic target. Additionally, future research could explore the interaction between BCoR and other POZ proteins and its potential role in other diseases.
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