Department of Molecular Cell Biology and Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.
Department of Biochemistry and Molecular Biology, University of Ulsan, College of Medicine, Seoul 05505, Korea.
BMB Rep. 2021 Aug;54(8):413-418. doi: 10.5483/BMBRep.2021.54.8.022.
ErbB3-binding protein 1 (EBP1) is a multifunctional protein associated with neural development. Loss of Ebp1 leads to upregulation of the gene silencing unit suppressor of variegation 3-9 homolog 1 (Suv39H1)/DNA (cytosine 5)-methyltransferase (DNMT1). EBP1 directly binds to the promoter region of DNMT1, repressing DNA methylation, and hence, promoting neural development. In the current study, we showed that EBP1 suppresses histone methyltransferase activity of Suv39H1 by promoting ubiquitin-proteasome system (UPS)-dependent degradation of Suv39H1. In addition, we showed that EBP1 directly interacts with Suv39H1, and this interaction is required for recruiting the E3 ligase MDM2 for Suv39H1 degradation. Thus, our findings suggest that EBP1 regulates UPS-dependent degradation of Suv39H1 to govern proper heterochromatin assembly during neural development. [BMB Reports 2021; 54(8): 413-418].
ErbB3 结合蛋白 1（EBP1）是一种与神经发育相关的多功能蛋白。Ebp1 的缺失导致基因沉默单元抑制斑驳 3-9 同源物 1（Suv39H1）/DNA（胞嘧啶 5）-甲基转移酶（DNMT1）的上调。EBP1 直接结合到 DNMT1 的启动子区域，抑制 DNA 甲基化，从而促进神经发育。在本研究中，我们表明 EBP1 通过促进泛素-蛋白酶体系统（UPS）依赖性的 Suv39H1 降解来抑制 Suv39H1 的组蛋白甲基转移酶活性。此外，我们表明 EBP1 与 Suv39H1 直接相互作用，这种相互作用对于招募 E3 连接酶 MDM2 进行 Suv39H1 降解是必需的。因此，我们的研究结果表明，EBP1 调节 Suv39H1 的 UPS 依赖性降解，以在神经发育过程中调节适当的异染色质组装。[BMB 报告 2021；54(8): 413-418]。
