Specific cleavage of the nuclear pore complex protein Nup62 by a viral protease

Nogi Park, Tim Skern, Kurt E. Gustin

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

Previous work has shown that several nucleoporins, including Nup62 are degraded in cells infected with human rhinovirus (HRV) and poliovirus (PV) and that this contributes to the disruption of certain nuclear transport pathways. In this study, the mechanisms underlying proteolysis of Nup62 have been investigated. Analysis of Nup62 in lysates from HRV-infected cells revealed that Nup62 was cleaved at multiple sites during viral infection. The addition of purified HRV2 2A protease (2Apro) to uninfected HeLa whole cell lysates resulted in the cleavage of Nup62, suggesting that 2Apro is a major contributor to Nup62 processing. The ability of purified 2Apro to cleave bacterially expressed and purified Nup62 demonstrated that 2A pro directly cleaves Nup62 in vitro. Site-directed mutagenesis of putative cleavage sites in Nup62 identified six different positions that are cleaved by 2Apro in vitro. This analysis revealed that 2A pro cleavage sites were located between amino acids 103 and 298 in Nup62 and suggested that the N-terminal FG-rich region of Nup62 was released from the nuclear pore complex in infected cells. Analysis of HRV- and PV-infected cells using domain-specific antibodies confirmed that this was indeed the case. These results are consistent with a model whereby PV and HRV disrupt nucleo-cytoplasmic trafficking by selectively removing FG repeat domains from a subset of nuclear pore complex proteins.

Original languageEnglish (US)
Pages (from-to)28796-28805
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number37
DOIs
StatePublished - Sep 10 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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