Leprêtre Chloé, Fleurier Yves, Martin Elisabeth, Torriglia Alicia
Université Pierre et Marie Curie, Paris, France.
Biochim Biophys Acta. 2008 Jun;1783(6):1068-75. doi: 10.1016/j.bbamcr.2008.02.012. Epub 2008 Feb 23.
LEI/L-DNase II is the key protein of a caspase-independent pathway activated by serine proteases. LEI (Leukocyte elastase inhibitor), L-DNase II precursor, is a member of the clade B serpins (also called serpin b1). In its native conformation it inhibits several intracellular proteases and has an anti-apoptotic activity. Following a metabolic stress and the increase of protease activity in the cell, LEI is cleaved and transformed into L-DNase II (LEI-derived DNase II). This transformation is due to a conformational modification that exposes a nuclear localization signal and an endonuclease active site. In this paper we show that LEI can bind the exportin Crm1, and we identify on LEI a nuclear export signal involved in the control of LEI/L-DNase II nuclearization in healthy cells. Point mutation of this site increases the accumulation of the molecule in the nucleus and triggers cell death.
LEI/L - 脱氧核糖核酸酶II是丝氨酸蛋白酶激活的非半胱天冬酶依赖性途径的关键蛋白。LEI（白细胞弹性蛋白酶抑制剂），即L - 脱氧核糖核酸酶II前体，是进化枝B丝氨酸蛋白酶抑制剂（也称为丝氨酸蛋白酶抑制剂b1）的成员。在其天然构象中，它抑制多种细胞内蛋白酶并具有抗凋亡活性。在代谢应激和细胞内蛋白酶活性增加后，LEI被切割并转化为L - 脱氧核糖核酸酶II（源自LEI的脱氧核糖核酸酶II）。这种转化是由于构象修饰暴露了核定位信号和核酸内切酶活性位点。在本文中，我们表明LEI可以结合核输出蛋白Crm1，并且我们在LEI上鉴定出一个核输出信号，该信号参与健康细胞中LEI/L - 脱氧核糖核酸酶II的核化控制。该位点的点突变增加了分子在细胞核中的积累并引发细胞死亡。
