Anuj Sharma - SARS-CoV 9b protein diffuses into nucleus, undergoes active Crm1 mediated nucleocytoplasmic export and triggers apoptosis when retained in the nucleus.

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      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.   PRINCIPAL FINDINGS/METHODOLOGY: 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. CONCLUSION/SIGNIFICANCE:   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.

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