MEF2B mutations lead to deregulated expression of the oncogene BCL6 in diffuse large B cell lymphoma
Open Access
- 25 August 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 14 (10), 1084-1092
- https://doi.org/10.1038/ni.2688
Abstract
Diffuse large B cell lymphomas can arise from dysregulation of BCL6 expression. Dalla-Favera and colleagues show that the transcription factor MEF2B regulates BCL6 and is commonly associated with the generation of such lymphomas. MEF2B encodes a transcriptional activator and is mutated in ∼11% of diffuse large B cell lymphomas (DLBCLs) and ∼12% of follicular lymphomas (FLs). Here we found that MEF2B directly activated the transcription of the proto-oncogene BCL6 in normal germinal-center (GC) B cells and was required for DLBCL proliferation. Mutation of MEF2B resulted in enhanced transcriptional activity of MEF2B either through disruption of its interaction with the corepressor CABIN1 or by rendering it insensitive to inhibitory signaling events mediated by phosphorylation and sumoylation. Consequently, the transcriptional activity of Bcl-6 was deregulated in DLBCLs with MEF2B mutations. Thus, somatic mutations of MEF2B may contribute to lymphomagenesis by deregulating BCL6 expression, and MEF2B may represent an alternative target for blocking Bcl-6 activity in DLBCLs.Keywords
This publication has 61 references indexed in Scilit:
- A tumour suppressor network relying on the polyamine–hypusine axisNature, 2012
- Combined Genetic Inactivation of β2-Microglobulin and CD58 Reveals Frequent Escape from Immune Recognition in Diffuse Large B Cell LymphomaCancer Cell, 2011
- Functional Identification of Optimized RNAi Triggers Using a Massively Parallel Sensor AssayMolecular Cell, 2011
- Inactivating mutations of acetyltransferase genes in B-cell lymphomaNature, 2011
- A Small-Molecule Inhibitor of BCL6 Kills DLBCL Cells In Vitro and In VivoCancer Cell, 2010
- A human B‐cell interactome identifies MYB and FOXM1 as master regulators of proliferation in germinal centersMolecular Systems Biology, 2010
- Mutations of multiple genes cause deregulation of NF-κB in diffuse large B-cell lymphomaNature, 2009
- Transcription factor Mef2c is required for B cell proliferation and survival after antigen receptor stimulationNature Immunology, 2008
- Reverse engineering of regulatory networks in human B cellsNature Genetics, 2005
- Distinct types of diffuse large B-cell lymphoma identified by gene expression profilingNature, 2000