Interaction of the Hepatitis B Virus X Protein with the Crm1-dependent Nuclear Export Pathway

Marshonna Forgues, Aizen J. Marrogi, Elisa A. Spillare, Chuan Ging Wu, Qin Yang, Minoru Yoshida, Xin Wei Wang

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79 Scopus citations


The leucine-rich nuclear export signal (NES) is used to shuttle large cellular proteins from the nucleus to the cytoplasm. The nuclear export receptor Crm1 is essential in this process by recognizing the NES motif. Here, we show that the oncogenic hepatitis B virus (HBV) X protein (HBx) contains a functional NES motif. We found that the predominant cytoplasmic localization of HBx is sensitive to the drug leptomycin B (LMB), which specifically inactivates Crm1. Mutations at the two conserved leucine residues to alanine at the NES motif (L98A,L100A) resulted in a nuclear redistribution of HBx. A recombinant HBx protein binds to Crm1 in vitro. In addition, ectopic expression of HBx sequesters Crm1 in the cytoplasm. Furthermore, HBx activates NFκB by inducing its nuclear translocation in a NES-dependent manner. Abnormal cytoplasmic sequestration of Crm1, accompanied by a nuclear localization of NFκB, was also observed in hepatocytes from HBV-positive liver samples with chronic active hepatitis. We suggest that Crm1 may play a role in HBx-mediated liver carcinogenesis.

Original languageEnglish
Pages (from-to)22797-22803
Number of pages7
JournalJournal of Biological Chemistry
Issue number25
StatePublished - Jun 22 2001


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