Nuclear export of LEI/L-DNase II by Crm1 is essential for cell survival
- 作者：Chloé ; Leprê ; tre ; Yves Fleurier ; Elisabeth Martin ; Alicia Torriglia
- 关键词：LEI ; L-DNase II ; NES ; Apoptosis ; Caspase-independent ; Serpin
- 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
- 出版年：2008
- 期刊代码：20_01674889
- 类别：bio
- 出版时间：June 2008
- 卷：1783
- 期：6
- 页码：1068-1075
- 文件大小：970 K
摘要
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.