Nuclear export of LEI/L-DNase II by Crm1 is essential for cell survival.
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.
Leprêtre
Chloé
C
Université Pierre et Marie Curie, Paris, France.
Fleurier
Yves
Y
Martin
Elisabeth
E
Torriglia
Alicia
A
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D006224:Cricetinae; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D047468:Immunoprecipitation; D028884:Karyopherins / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000502:physiology*; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D019913:Nuclear Localization Signals; D017354:Point Mutation; D011487:Protein Conformation; D053491:Proteinase Inhibitory Proteins, Secretory; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism*; D000097606:Exportin 1 Protein
D004706:Endodeoxyribonucleases; D028884:Karyopherins; D019272:Leukocyte Elastase; D019913:Nuclear Localization Signals; D053491:Proteinase Inhibitory Proteins, Secretory; D018160:Receptors, Cytoplasmic and Nuclear; D015842:Serine Proteinase Inhibitors; D015843:Serpins; D000097606:Exportin 1 Protein; C019329:deoxyribonuclease II