EBP1 regulates Suv39H1 stability via the ubiquitin-proteasome system in neural development
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초록
ErbB3-binding protein 1 (EBP1) is a multifunctional protein associatedwith neural development. Loss of Ebp1 leads to upregulationof the gene silencing unit suppressor of variegation3-9 homolog 1 (Suv39H1)/DNA (cytosine 5)-methyltransferase(DNMT1). EBP1 directly binds to the promoter region of DNMT1,repressing DNA methylation, and hence, promoting neuraldevelopment. In the current study, we showed that EBP1suppresses histone methyltransferase activity of Suv39H1 bypromoting ubiquitin-proteasome system (UPS)-dependent degradationof Suv39H1. In addition, we showed that EBP1 directlyinteracts with Suv39H1, and this interaction is required forrecruiting the E3 ligase MDM2 for Suv39H1 degradation. Thus, our findings suggest that EBP1 regulates UPS-dependentdegradation of Suv39H1 to govern proper heterochromatinassembly during neural development.
Abstract
ErbB3-binding protein 1 (EBP1) is a multifunctional protein associatedwith neural development. Loss of Ebp1 leads to upregulationof the gene silencing unit suppressor of variegation3-9 homolog 1 (Suv39H1)/DNA (cytosine 5)-methyltransferase(DNMT1). EBP1 directly binds to the promoter region of DNMT1,repressing DNA methylation, and hence, promoting neuraldevelopment. In the current study, we showed that EBP1suppresses histone methyltransferase activity of Suv39H1 bypromoting ubiquitin-proteasome system (UPS)-dependent degradationof Suv39H1. In addition, we showed that EBP1 directlyinteracts with Suv39H1, and this interaction is required forrecruiting the E3 ligase MDM2 for Suv39H1 degradation. Thus, our findings suggest that EBP1 regulates UPS-dependentdegradation of Suv39H1 to govern proper heterochromatinassembly during neural development.
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