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
Abstract
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.
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BCL6 represses a broad range of genes involved in the DNA damage response, cell cycle checkpoints, and differentiation.
“BCL6 represses a broad range of genes involved in the DNA damage response18, cell cycle checkpoints19, and differentiation20.”
From Small-molecule-induced polymerization triggers degradation of BCL6 (2020) · cites this paper as [20]
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References 50 · Cited by 343
- Authors
- Phan, R. T., Saito, M., Basso, K., Niu, H., & Dalla-Favera, R.
- Affiliations
- Harvard University (US)
- Herbert Irving Comprehensive Cancer Center (US)
- Venue
- Nature Immunology
- Published
- 2005-09-04
- Volume
- 6
- Issue
- 10
- Pages
- 1054-1060
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2076543297
- Cited by
- 343
- References
- 50
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 6 · 2023: 12 · 2022: 12 · 2021: 13 · 2020: 15 · 2019: 10 · 2018: 17 · 2017: 15 · 2016: 19 · 2015: 11 · 2014: 18 · 2013: 13 · 2012: 25
- FWCI
- 13.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- BCL6, Miz-1, p21, cell cycle arrest, germinal center B cells, transcriptional repression, transcriptional activation, B-cell lymphoma, lymphomagenesis, transcription factor interaction
- MeSH terms
- Proto-Oncogene Mas, B-Lymphocytes, Cell Cycle, Cell Division, Cell Line, DNA-Binding Proteins, Enzyme Inhibitors, Humans, Molecular Sequence Data, Promoter Regions, Genetic, Proto-Oncogene Proteins, Transcription Factors, Transcription, Genetic, Zinc Fingers, Cell Cycle Proteins, Germinal Center, Cyclin-Dependent Kinase Inhibitor p21, Proto-Oncogene Proteins c-bcl-6, Kruppel-Like Transcription Factors
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