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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.

SUBMITTER: Ying CY 

PROVIDER: S-EPMC3954820 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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MEF2B mutations lead to deregulated expression of the oncogene BCL6 in diffuse large B cell lymphoma.

Ying Carol Y CY   Dominguez-Sola David D   Fabi Melissa M   Lorenz Ivo C IC   Hussein Shafinaz S   Bansal Mukesh M   Califano Andrea A   Pasqualucci Laura L   Basso Katia K   Dalla-Favera Riccardo R  

Nature immunology 20130825 10

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 in  ...[more]

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