title: SARS-CoV 9b protein diffuses into nucleus, undergoes active Crm1 mediated nucleocytoplasmic export and triggers apoptosis when retained in the nucleus.
abstract: BACKGROUND
  9b is an accessory protein of the SARS-CoV. It is a small protein of 98 amino acids and its structure has been solved recently. 9b is known to localize in the extra-nuclear region and has been postulated to possess a nuclear export signal (NES), however the role of NES in 9b functioning is not well understood.
  
  
  RESULTS
  In this report, we demonstrate that 9b in the absence of any nuclear localization signal (NLS) enters the nucleus by passive transport. Using various cell cycle inhibitors, we have shown that the nuclear entry of 9b is independent of the cell cycle. Further, we found that 9b interacts with the cellular protein Crm1 and gets exported out of the nucleus using an active NES. We have also revealed that this NES activity influences the half-life of 9b and affects host cell death. We found that an export signal deficient SARS-CoV 9b protein induces apoptosis in transiently transfected cells and showed elevated caspase-3 activity.
  
  
  CONCLUSIONS
  Here, we showed that nuclear shuttling of 9b and its interaction with Crm1 are essential for the proper degradation of 9b and blocking the nuclear export of this protein induces apoptosis. This phenomenon may be critical in providing a novel role to the 9b accessory protein of SARS-CoV.
authors.affiliation: Virology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors.forename: Kulbhushan
authors.initials: K
authors.lastname: Sharma
authors.forename: Sara
authors.initials: S
authors.lastname: Åkerström
authors.forename: Anuj Kumar
authors.initials: AK
authors.lastname: Sharma
authors.forename: Vincent T K
authors.initials: VT
authors.lastname: Chow
authors.forename: Shumein
authors.initials: S
authors.lastname: Teow
authors.forename: Bernard
authors.initials: B
authors.lastname: Abrenica
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Booth
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Booth
authors.forename: Ali
authors.initials: A
authors.lastname: Mirazimi
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Lal
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004058:Diffusion; D042541:Intracellular Space / Q000378:metabolism; D028884:Karyopherins / Q000378:metabolism*; D008954:Models, Biological; D049790:Nuclear Export Signals; D019913:Nuclear Localization Signals / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism*; D014162:Transfection; D014709:Vero Cells; D014764:Viral Proteins / Q000378:metabolism*; D000097606:Exportin 1 Protein
chemical_list: D028884:Karyopherins; D049790:Nuclear Export Signals; D019913:Nuclear Localization Signals; D018160:Receptors, Cytoplasmic and Nuclear; D014764:Viral Proteins; D000097606:Exportin 1 Protein