Specific Cleavage of the Nuclear Pore Complex Protein Nup62 by a Viral Protease

Park, Nogi; Skern, Tim; Gustin, Kurt E.

doi:10.1074/jbc.m110.143404

Cited by 88 publications

(102 citation statements)

References 50 publications

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“…Subsequently, we learned that an annotation cluster-labeled nuclear pore that included Nup62 ranked fourth out of 76 enriched functional groups in the siRNA screen of Mercer et al (20). Moreover, Nup62 has been shown to interact directly with herpes simplex virus ICP27 (40) and Epstein Barr virus BGLF-4 (41) and to be degraded by poliovirus and rhinovirus proteases (42). We found that knockdown of Nup62 inhibited the production of infectious VACV in a one-step growth experiment, but had no effect on entry and only modest effects on DNA replication and early and late viral gene expression.…”

Section: Discussionmentioning

confidence: 99%

Human genome-wide RNAi screen reveals a role for nuclear pore proteins in poxvirus morphogenesis

Sivan

Martin

Myers

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Poxviruses are considered less dependent on host functions than other DNA viruses because of their cytoplasmic site of replication and large genomes, which encode enzymes for DNA and mRNA synthesis. Nevertheless, RNAi screens with two independent human genome-scale libraries have identified more than 500 candidate genes that significantly inhibited and a similar number that enhanced replication and spread of infectious vaccinia virus (VACV). Translational, ubiquitin-proteosome, and endoplasmic reticulum-to-Golgi transport functions, known to be important for VACV, were enriched in the siRNA-inhibiting group, and RNA polymerase II and associated functions were enriched in the siRNAenhancing group. Additional findings, notably the inhibition of VACV spread by siRNAs to several nuclear pore genes, were unanticipated. Knockdown of nucleoporin 62 strongly inhibited viral morphogenesis, with only a modest effect on viral gene expression, recapitulating and providing insight into previous studies with enucleated cells.

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Section: Discussionmentioning

confidence: 99%

Human genome-wide RNAi screen reveals a role for nuclear pore proteins in poxvirus morphogenesis

Sivan

Martin

Myers

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…This is noticed at the level of transcription, mRNA processing, nucleocytoplasmic transport, translation, or RNA granules composition. Among other proteins, proteolysis affects splicing factors, RNAprocessing proteins, RNA helicases, nuclear pore factors, stress granules assembly factors or antiviral response proteins (Almstead and Sarnow, 2007;Barral et al, 2009;Castello et al, 2009;Chen et al, 2013;Lawrence et al, 2012;Mukherjee et al, 2011;Park et al, 2010;Pineiro et al, 2012;Rozovics et al, 2012;Shiroki et al, 1999;Watters and Palmenberg, 2011;Weng et al, 2009;White et al, 2007).…”

Section: Picornavirus-induced Modification Of Host Factorsmentioning

confidence: 99%

Picornavirus IRES elements: RNA structure and host protein interactions

et al. 2015

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“…Expression of poliovirus 2A proteinase in uninfected cells causes the cytoplasmic relocalization of some host nuclear factors, initially suggesting that 2A may be responsible for the degradation of nuclear pore complex proteins (or Nups) during infection (14). Specific Nups are cleaved during poliovirus or human rhinovirus infection, which results in the disruption of certain import/export pathways (15)(16)(17)(18)(19)(20). More recent work has demonstrated that poliovirus and human rhinovirus 2A proteinases can directly cleave specific Nups (17,18,20,21).…”

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confidence: 99%

Viral Proteinase Requirements for the Nucleocytoplasmic Relocalization of Cellular Splicing Factor SRp20 during Picornavirus Infections

Fitzgerald

Chase

Cathcart

et al. 2013

J Virol

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Infection of mammalian cells by picornaviruses results in the nucleocytoplasmic redistribution of certain host cell proteins. These viruses interfere with import-export pathways, allowing for the cytoplasmic accumulation of nuclear proteins that are then available to function in viral processes. We recently described the cytoplasmic relocalization of cellular splicing factor SRp20 during poliovirus infection. SRp20 is an important internal ribosome entry site (IRES) trans-acting factor (ITAF) for poliovirus IRES-mediated translation; however, it is not known whether other picornaviruses utilize SRp20 as an ITAF and direct its cytoplasmic relocalization. Also, the mechanism by which poliovirus directs the accumulation of SRp20 in the cytoplasm of the infected cell is currently unknown. Work described in this report demonstrated that infection by another picornavirus (coxsackievirus B3) causes SRp20 to relocalize from the nucleus to the cytoplasm of HeLa cells, similar to poliovirus infection; however, SRp20 is relocalized to a somewhat lesser extent in the cytoplasm of HeLa cells during infection by yet another picornavirus (human rhinovirus 16). We show that expression of poliovirus 2A proteinase is sufficient to cause the nucleocytoplasmic redistribution of SRp20. Following expression of poliovirus 2A proteinase in HeLa cells, we detect cleavage of specific nuclear pore proteins known to be cleaved during poliovirus infection. We also find that expression of human rhinovirus 16 2A proteinase alone can cause efficient cytoplasmic relocalization of SRp20, despite the lower levels of SRp20 relocalization observed during rhinovirus infection compared to poliovirus. Taken together, these results further define the mechanism of SRp20 cellular redistribution during picornavirus infections, and they provide additional insight into some of the differences observed between human rhinovirus and other enterovirus infections. Members of the Picornaviridae family of viruses cause a range of diseases in humans, including poliomyelitis, myocarditis, and the common cold. Picornaviruses are small single-stranded, positive-sense RNA viruses that include the enteroviruses poliovirus and coxsackievirus, as well as human rhinoviruses (HRVs). They contain a ϳ7.0-kb-to-8.5-kb genome that consists of a single open reading frame, which is translated to generate a polyprotein that is proteolytically processed by viral proteinases into structural and nonstructural proteins. Instead of a 7-methyl guanosine cap structure, picornaviruses contain a small viral protein, VPg, covalently linked to the 5= end of the RNA. This unique protein-RNA linkage serves as a primer for viral RNA synthesis. Viral translation occurs via a cap-independent mechanism and is driven by an internal ribosome entry site (IRES) located in the long, highly structured 5= noncoding region (5= NCR).In addition to proteolytic processing of the viral polyprotein, the viral proteinases 2A and 3C/3CD cleave several cellular proteins, including eukaryotic initiation factor 4G ...

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Specific Cleavage of the Nuclear Pore Complex Protein Nup62 by a Viral Protease

Cited by 88 publications

References 50 publications

Human genome-wide RNAi screen reveals a role for nuclear pore proteins in poxvirus morphogenesis

Human genome-wide RNAi screen reveals a role for nuclear pore proteins in poxvirus morphogenesis

Picornavirus IRES elements: RNA structure and host protein interactions

Viral Proteinase Requirements for the Nucleocytoplasmic Relocalization of Cellular Splicing Factor SRp20 during Picornavirus Infections

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