BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cells
Copyright policy )BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cells
The BCL6 proto-oncogene encodes a transcriptional repressor that is required for germinal center formation and has been linked to lymphomagenesis. BCL6 functions by directly binding to specific DNA sequences and suppressing the transcription of target genes. Here we report an alternative mechanism by which BCL6 controls the transcription of genes lacking a BCL6 binding site and show that this mechanism was required for the prevention of tumor suppressor p53-independent cell cycle arrest in germinal center B cells. BCL6 interacted with the transcriptional activator Miz-1 and, via Miz-1, bound to the promoter and suppressed transcription of the cell cycle arrest gene CDKN1A. Through this mechanism, BCL6 may facilitate the proliferative expansion of germinal centers during the normal immune response and, when deregulated, the pathological expansion of B cell lymphomas.
- Columbia University United States
- King’s University United States
- Roche (United States) United States
- Herbert Irving Comprehensive Cancer Center United States
- Roche Institute of Molecular Biology United States
Cyclin-Dependent Kinase Inhibitor p21, B-Lymphocytes, Transcription, Genetic, Cell Cycle, Molecular Sequence Data, Kruppel-Like Transcription Factors, Cell Cycle Proteins, Zinc Fingers, Germinal Center, Proto-Oncogene Mas, Cell Line, DNA-Binding Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-6, Humans, Enzyme Inhibitors, Promoter Regions, Genetic, Cell Division, Transcription Factors
Cyclin-Dependent Kinase Inhibitor p21, B-Lymphocytes, Transcription, Genetic, Cell Cycle, Molecular Sequence Data, Kruppel-Like Transcription Factors, Cell Cycle Proteins, Zinc Fingers, Germinal Center, Proto-Oncogene Mas, Cell Line, DNA-Binding Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-6, Humans, Enzyme Inhibitors, Promoter Regions, Genetic, Cell Division, Transcription Factors
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