核输入途径是拯救显性早老素表型的关键。
Nuclear import pathway key to rescuing dominant progerin phenotypes.
机构信息
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Email:
出版信息
Sci Signal. 2018 Jul 3;11(537):eaat9448. doi: 10.1126/scisignal.aat9448.
Abstract
In this issue of , Larrieu show that an acetyltransferase inhibitor that rescues many dominant nuclear phenotypes caused by progerin, a truncated form of lamin A, does so by releasing the specialized nuclear import receptor TNPO1 from sequestration by microtubules. This release enables TNPO1-dependent import of specific cargoes, including the nuclear pore protein Nup153 and the heterogeneous nuclear ribonucleoprotein hnRNPA1, thus restoring the functionality of nuclear pore complexes, rebalancing the nucleocytoplasmic Ran gradient, and normalizing gene expression.
摘要
在本期 中，Larrieu 等人表明，一种乙酰转移酶抑制剂可以通过将特殊的核输入受体 TNPO1 从微管隔离中释放出来，从而挽救由 lamin A 的截断形式 progerin 引起的许多显性核表型。这种释放使 TNPO1 依赖的特定货物的输入成为可能，包括核孔蛋白 Nup153 和异质核核糖核蛋白 hnRNPA1，从而恢复核孔复合物的功能，重新平衡核质 Ran 梯度，并使基因表达正常化。
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