| EBP1 regulates Suv39H1 stability via the ubiquitin-proteasome system in neural development |
Byeong-Seong Kim1,2 (Graduate student), Hyo Rim Ko1,2 (Ph.D), Inwoo Hwang1,2 (Graduate student), Sung-Woo Cho3 (Professor), Jee-Yin Ahn  1,2,4,* (Professor) |
1Department of Molecular Cell biology and 2Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea,
3Department of Biochemistry and Molecular Biology, University of Ulsan, College of Medicine, Seoul 05505, Korea,
4Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Korea |
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Abstract
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.
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| Abstract, Accepted Manuscript(in press) [Submitted on February 16, 2021, Accepted on March 8, 2021] |
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