Institute for Cancer Genetics, Columbia University, New York, New York, USA.
Nat Immunol. 2013 Oct;14(10):1084-92. doi: 10.1038/ni.2688. Epub 2013 Aug 25.
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.
MEF2B 编码一种转录激活因子，在约 11%的弥漫性大 B 细胞淋巴瘤（DLBCL）和约 12%的滤泡性淋巴瘤（FL）中发生突变。在这里，我们发现 MEF2B 可直接激活正常生发中心（GC）B 细胞中原癌基因 BCL6 的转录，并且是 DLBCL 增殖所必需的。MEF2B 的突变通过破坏其与共抑制因子 CABIN1 的相互作用或使其对由磷酸化和 sumoylation 介导的抑制信号事件不敏感，导致 MEF2B 的转录活性增强。因此，MEF2B 突变的 DLBCL 中 Bcl-6 的转录活性被失调。因此，MEF2B 的体细胞突变可能通过失调 BCL6 的表达而导致淋巴瘤的发生，并且 MEF2B 可能代表用于阻断 DLBCL 中 Bcl-6 活性的另一个靶标。
