Nature Immunology
6, 1054 - 1060 (2005)
Published online: 4 September 2005; | doi:10.1038/ni1245
BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cellsRyan T Phan1, 2, Masumichi Saito1, Katia Basso1, Huifeng Niu1, 2
& Riccardo Dalla-Favera11
Institute for Cancer Genetics, Department of Pathology, Department of Genetics and Development and the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York 10032, USA. 2
Present addresses: Children's Hospital, Center for Blood Research, Harvard University Medical School, Boston, Massachusetts 02115, USA (R.T.P.), and Roche Institute of Molecular Biology, Nutley, New Jersey 07110, USA (H.N.).
Correspondence should be addressed to Riccardo Dalla-Favera rd10@columbia.edu 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.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated. NEWS AND VIEWSA-Miz-ing BCL6Nature Immunology News and Views (01 Oct 2005)
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