title: MEF2B mutations lead to deregulated expression of the oncogene BCL6 in diffuse large B cell lymphoma.
abstract: 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.
authors: Institute for Cancer Genetics, Columbia University, New York, New York, USA.
authors: Carol Y
authors: CY
authors: Ying
authors: David
authors: D
authors: Dominguez-Sola
authors: Melissa
authors: M
authors: Fabi
authors: Ivo C
authors: IC
authors: Lorenz
authors: Shafinaz
authors: S
authors: Hussein
authors: Mukesh
authors: M
authors: Bansal
authors: Andrea
authors: A
authors: Califano
authors: Laura
authors: L
authors: Pasqualucci
authors: Katia
authors: K
authors: Basso
authors: Riccardo
authors: R
authors: Dalla-Favera
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation; D016000:Cluster Analysis; D019295:Computational Biology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism; D026161:MADS Domain Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D064326:MEF2 Transcription Factors; D051379:Mice; D062105:Molecular Docking Simulation; D009154:Mutation; D018006:Myogenic Regulatory Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D000090063:Proto-Oncogene Mas; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics*; D058207:Sumoylation / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491861:CABIN1 protein, human; D026161:MADS Domain Proteins; C000715470:MAS1 protein, human; D064326:MEF2 Transcription Factors; C578038:MEF2B protein, human; D018006:Myogenic Regulatory Factors; D000090063:Proto-Oncogene Mas; D051560:Proto-Oncogene Proteins c-bcl-6; D017868:Cyclic AMP-Dependent Protein Kinases
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