Centromeres are chromosomal loci marked by histone variant Cen H3(centromeric histone H3)and essential for genomic stability and cell division.The budding yeast E3 ubiquitin ligase Psh1 selectively recognizes the yeas...Centromeres are chromosomal loci marked by histone variant Cen H3(centromeric histone H3)and essential for genomic stability and cell division.The budding yeast E3 ubiquitin ligase Psh1 selectively recognizes the yeast Cen H3(Cse4)for ubiquitination and controls the cellular level of Cse4 for proteolysis,but the underlying mechanism remains largely unknown.Here,we show that Psh1 uses a Cse4-binding domain(CBD,residues 1-211)to interact with Cse4-H4 instead of H3-H4,yielding a dissociation constant(Kd)of 27 nM.Psh1 recognizes Cse4-specific residues in the L1 loop and a2 helix to ensure Cse4 binding and ubiquitination.We map the Psh1-binding region of Cse4-H4 and identify a wide range of Cse4-specific residues required for the Psh1-mediated Cse4 recognition and ubiquitination.Further analyses reveal that histone chaperone Scm3 can impair Cse4 ubiquitination by abrogating Psh1-Cse4 binding.Together,our study reveals a novel Cse4-binding mode distinct from those of known Cen H3 chaperones and elucidates the mechanism by which Scm3 competes with Psh1 for Cse4 binding.展开更多
本文研究了沙棘籽渣多糖(Polysaccharides from seed residue of Hippophae rhamnoide L.,PSH)对正常小鼠及实验性2型糖尿病大鼠血糖、血脂代谢的影响。以100、200和400 mg/kg剂量的PSH连续灌胃正常小鼠20d;以50和100 mg/kg剂量的PSH连...本文研究了沙棘籽渣多糖(Polysaccharides from seed residue of Hippophae rhamnoide L.,PSH)对正常小鼠及实验性2型糖尿病大鼠血糖、血脂代谢的影响。以100、200和400 mg/kg剂量的PSH连续灌胃正常小鼠20d;以50和100 mg/kg剂量的PSH连续灌胃由烟酰胺联合链脲佐菌素诱导的类似2型糖尿病大鼠3周,测定血糖、糖基化血清蛋白、血清胰岛素、血清总胆固醇、甘油三酯及肝糖原含量。结果显示:PSH对正常小鼠的血糖和血脂代谢没有明显影响;但能明显降低2型糖尿病大鼠的血清葡萄糖、总胆固醇和糖基化血清蛋白水平,同时显著增加糖尿病大鼠的血清胰岛素含量。上述结果表明:PSH在实验性2型糖尿病大鼠模型上具有降血糖和降胆固醇的活性。展开更多
基金supported by the grants from Natural Science Foundation of China(31521002,31970621,31871318,31671344,31801070)National Key Research and Development Program of China(2019YFA0508902)Strategic Priority Research Program(XDB37010100)。
文摘Centromeres are chromosomal loci marked by histone variant Cen H3(centromeric histone H3)and essential for genomic stability and cell division.The budding yeast E3 ubiquitin ligase Psh1 selectively recognizes the yeast Cen H3(Cse4)for ubiquitination and controls the cellular level of Cse4 for proteolysis,but the underlying mechanism remains largely unknown.Here,we show that Psh1 uses a Cse4-binding domain(CBD,residues 1-211)to interact with Cse4-H4 instead of H3-H4,yielding a dissociation constant(Kd)of 27 nM.Psh1 recognizes Cse4-specific residues in the L1 loop and a2 helix to ensure Cse4 binding and ubiquitination.We map the Psh1-binding region of Cse4-H4 and identify a wide range of Cse4-specific residues required for the Psh1-mediated Cse4 recognition and ubiquitination.Further analyses reveal that histone chaperone Scm3 can impair Cse4 ubiquitination by abrogating Psh1-Cse4 binding.Together,our study reveals a novel Cse4-binding mode distinct from those of known Cen H3 chaperones and elucidates the mechanism by which Scm3 competes with Psh1 for Cse4 binding.
文摘本文研究了沙棘籽渣多糖(Polysaccharides from seed residue of Hippophae rhamnoide L.,PSH)对正常小鼠及实验性2型糖尿病大鼠血糖、血脂代谢的影响。以100、200和400 mg/kg剂量的PSH连续灌胃正常小鼠20d;以50和100 mg/kg剂量的PSH连续灌胃由烟酰胺联合链脲佐菌素诱导的类似2型糖尿病大鼠3周,测定血糖、糖基化血清蛋白、血清胰岛素、血清总胆固醇、甘油三酯及肝糖原含量。结果显示:PSH对正常小鼠的血糖和血脂代谢没有明显影响;但能明显降低2型糖尿病大鼠的血清葡萄糖、总胆固醇和糖基化血清蛋白水平,同时显著增加糖尿病大鼠的血清胰岛素含量。上述结果表明:PSH在实验性2型糖尿病大鼠模型上具有降血糖和降胆固醇的活性。
