Abstract:
Myocyte enhancer factor 2 (MEF2) is a key transcription factor (TF) in skeletal, cardiac, and neural tissue development and includes four isoforms: MEF2A, MEF2B, MEF2C, and MEF2D. These isoforms significantly affect embryonic development, nervous system regulation, muscle cell differentiation, B- and T-cell development, thymocyte selection, and effects on tumorigenesis and leukemia. This chapter describes the multifaceted roles of MEF2 family proteins, covering embryonic development, nervous system regulation, and muscle cell differentiation. It further elucidates the contribution of MEF2 to various blood and immune cell functions. Specifically, in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), MEF2D is aberrantly expressed and forms a fusion protein with BCL9, CSF1R, DAZAP1, HNRNPUL1, and SS18. These fusion proteins are closely related to the pathogenesis of leukemia. In addition, it specifically introduces the regulatory effect of MEF2D fusion protein on the proliferation and growth of B-cell acute lymphoblastic leukemia (B-ALL) cells. Finally, we detail the positive feedback loop between MEF2D and IRF8 that significantly promotes the progression of acute myeloid leukemia (AML) and the importance of the ZMYND8-BRD4 interaction in regulating the IRF8 and MYC transcriptional programs. The MEF2D-CEBPE axis is highlighted as a key transcriptional mechanism controlling the block of leukemic cell self-renewal and differentiation in AML. This chapter starts with the structure and function of MEF2 family proteins, specifically summarizing and analyzing the role of MEF2D in B-ALL and AML, mediating the complex molecular mechanisms of transcriptional regulation and exploring their implications for human health and disease.
摘要:
肌细胞增强因子2(MEF2)是骨骼中的关键转录因子(TF),心脏,和神经组织发育,包括四个亚型:MEF2A,MEF2B,MEF2C,MEF2D这些亚型显著影响胚胎发育,神经系统调节,肌肉细胞分化,B细胞和T细胞发育,胸腺细胞选择,以及对肿瘤发生和白血病的影响。本章介绍了MEF2家族蛋白的多方面作用,涵盖胚胎发育,神经系统调节,和肌肉细胞分化。它进一步阐明了MEF2对各种血液和免疫细胞功能的贡献。具体来说,在B细胞前体急性淋巴细胞白血病(BCP-ALL)中,MEF2D异常表达并与BCL9,CSF1R,DAZAP1、HNRNPUL1和SS18。这些融合蛋白与白血病的发病机制密切相关。此外,它具体介绍了MEF2D融合蛋白对B细胞急性淋巴细胞白血病(B-ALL)细胞增殖和生长的调节作用。最后,我们详述了MEF2D和IRF8之间显著促进急性髓细胞性白血病(AML)进展的正反馈回路,以及ZMYND8-BRD4相互作用在调节IRF8和MYC转录程序中的重要性.MEF2D-CEBPE轴被强调为控制AML中白血病细胞自我更新和分化的阻断的关键转录机制。本章从MEF2家族蛋白的结构和功能开始,具体总结和分析MEF2D在B-ALL和AML中的作用,介导转录调控的复杂分子机制,并探索其对人类健康和疾病的影响。