Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28
Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28
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DOI：
10.1038/srep01381
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发表时间：
2013-03-05
影响因子：
4.6
通讯作者：
Nystrom, Thomas
中科院分区：
文献类型：
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作者：
Hernebring, Malin;Fredriksson, Asa;Nystrom, Thomas
在胚胎干细胞中，氧化损伤蛋白的去除是在细胞命运规范的第一个迹象时触发的，但其潜在机制尚不清楚。在这里，我们报告了分化阶段包括编码蛋白酶体激活因子PA28 α β (11S)、免疫蛋白酶体亚基（20Si）和20Si调节因子TNF α的基因的意外诱导。这种诱导伴随着成熟PA28-20S(i)蛋白酶体的组装和蛋白酶体活性的升高。使用miRNA抑制PA28 α的积累抵消了受损蛋白质的去除，这表明PA28 α β在从自我更新到细胞分化的过渡过程中，在重置蛋白质损伤水平方面具有迄今尚未确定的作用。
In embryonic stem cells, removal of oxidatively damaged proteins is triggered upon the first signs of cell fate specification but the underlying mechanism is not known. Here, we report that this phase of differentiation encompasses an unexpected induction of genes encoding the proteasome activator PA28 alpha beta (11S), subunits of the immunoproteasome (20Si), and the 20Si regulator TNF alpha. This induction is accompanied by assembly of mature PA28-20S(i) proteasomes and elevated proteasome activity. Inhibiting accumulation of PA28 alpha using miRNA counteracted the removal of damaged proteins demonstrating that PA28 alpha beta has a hitherto unidentified role required for resetting the levels of protein damage at the transition from self-renewal to cell differentiation.