title: mReg2 inhibits nuclear entry of apoptosis-inducing factor in mouse insulinoma cells.
abstract: We have reported earlier that murine-regenerating gene mReg2 protects MIN6 mouse insulinoma cells from ER stress and caspase-mediated apoptosis. In apoptotic cells, DNA damage is induced by the nuclear translocation of mitochondrial apoptosis-inducing factor (AIF). Here we tested the hypothesis that mReg2 may regulate Scythe and/or hsp70 which influence the nuclear import of AIF. Treatment with thapsigargin (Tg) or doxorubicin induced an increase in nuclear AIF in MIN6 cells carrying the empty transfection vector (MIN6-VC) but not in cells overexpressing mReg2 (MIN6-mReg2). On one hand, nuclear Scythe was higher in the nucleus of MIN6-mReg2 compared with that in MIN6-VC cells. mReg2 did not alter the expression of AIF or Scythe. On the other hand, mReg2 induced the expression of hsp70 which is known to promote cytosolic retention of AIF. We conclude that mReg2 inhibits AIF-mediated apoptosis by promoting the nuclear presence of Scythe and inducing hsp70.
authors.affiliation: Fraser Laboratories, Department of Medicine, McGill University Health Science Centre and Royal Victoria Hospital , Montreal, Quebec , Canada.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Subrata
authors.initials: S
authors.lastname: Chowdhury
authors.forename: Sadaf
authors.initials: S
authors.lastname: Uppal
authors.forename: Xin
authors.initials: X
authors.lastname: Fang
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Liu
authors.forename: Coimbatore B
authors.initials: CB
authors.lastname: Srikant
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051033:Apoptosis Inducing Factor; C484266:Bag6 protein, mouse; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C490253:Reg3b protein, mouse
keywords: AIF; MIN6 cells; apoptosis; hsp70; mReg2; scythe