Biophysical Characterization of Nucleophosmin Interactions with Human Immunodeficiency Virus Rev and Herpes Simplex Virus US11

Nouri, Kazem; Moll, Jens M.; Milroy, L.-G.; Hain, Anika; Dvorský, Radovan; Amin, Ehsan; Lenders, Michael H. H.; Nagel-Steger, Luitgard; Howe, Sebastian; Smits, Sander H. J.; Hengel, Hartmut; Schmitt, Lutz; Münk, Carsten; Brunsveld, Luc; Ahmadian, Mohammad Réza

doi:10.1371/journal.pone.0143634

Cited by 29 publications

(28 citation statements)

References 80 publications

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“…Two stretches of negatively charged amino acids in the primary structure of NPM1 are particularly important because these motifs may potentially bind with positively-charged amino acid stretches in viral proteins, such as arginine-rich motif (ARM) and NLS [ 51 ]. Viral positively charged amino acid sequences always play important regulatory roles in different stages of the viral replication cycle, such as nucleocytoplasmic transport, viral genome replication and transcription, and viral particle assembly [ 50 , 51 ]. However, whether PCV3 Cap, harboring a conserved NoLS, could also bind to NPM1 protein has not been reported.…”

Section: Discussionmentioning

confidence: 99%

The serine-48 residue of nucleolar phosphoprotein nucleophosmin-1 plays critical role in subcellular localization and interaction with porcine circovirus type 3 capsid protein

Zhou

et al. 2021

Vet Res

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The transport of circovirus capsid protein into nucleus is essential for viral replication in infected cell. However, the role of nucleolar shuttle proteins during porcine circovirus 3 capsid protein (PCV3 Cap) import is still not understood. Here, we report a previously unidentified nucleolar localization signal (NoLS) of PCV3 Cap, which hijacks the nucleolar phosphoprotein nucleophosmin-1 (NPM1) to facilitate nucleolar localization of PCV3 Cap. The NoLS of PCV3 Cap and serine-48 residue of N-terminal oligomerization domain of NPM1 are essential for PCV3 Cap/NPM1 interaction. In addition, charge property of serine-48 residue of NPM1 is critical for nucleolar localization and interaction with PCV3 Cap. Taken together, our findings demonstrate for the first time that NPM1 interacts with PCV3 Cap and is responsible for its nucleolar localization.

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Section: Discussionmentioning

confidence: 99%

The serine-48 residue of nucleolar phosphoprotein nucleophosmin-1 plays critical role in subcellular localization and interaction with porcine circovirus type 3 capsid protein

Zhou

et al. 2021

Vet Res

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“…NPM1, a versatile protein, interacts not only with multiple host cell factors, but also with different viral proteins. Because of its constitutive expression, intracellular dynamics, and binding capacities, NPM1 acts as a critical regulator of viral replication at different stages such as nuclear import, viral genome transcription and assembly, and particle formation [40][41][42][43]. In physiological conditions, NPM1 principally resides in the nucleolus, though it contains domains for cytoplasmic, nucleoplasmic, and nucleolar localization.…”

Section: Discussionmentioning

confidence: 99%

Nucleolar protein NPM1 is essential for circovirus replication by binding to viral capsid

et al. 2020

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Entry of circovirus into the host cell nucleus is essential for viral replication during the early stage of infection. However, the mechanisms by which nucleolar shuttle proteins are used during viral replication is still not well understood. Here, we report a previously unidentified nucleolar localization signal in circovirus capsid protein (Cap), and that circovirus hijacks the nucleolar phosphoprotein nucleophosmin-1 (NPM1) to facilitate its replication. Colocalization analysis showed that NPM1 translocates from the nucleolus to the nucleoplasm and cytoplasm during viral infection. Coimmunoprecipitation and glutathione S-transferase pull-down assays showed that Cap interacts directly with NPM1. Binding domain mapping showed that the arginine-rich N-terminal motif 1 MTYPRRRYRRRRHRPRSHLG 20 of Cap, and residue serine-48 of the N-terminal oligomerization domain of NPM1, are essential for the interaction. Virus rescue experiments showed that all arginine to alanine substitution in the N-terminal arginine-rich motif of Cap resulted in diminished viral replication. Knockdown of NPM1 and substitution of serine-48 in NPM1 to glutamic acid also decreased viral replication. In addition, binding assays showed that the arginine-rich motif of Cap is a nucleolar localization signal. Taken together, our findings demonstrate that circovirus protein Cap is a nucleolus-located, and regulates viral replication by directly binding to NPM1.

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“…NPM1 associates with viral proteins of different viruses and is implicated in various stages of viral infection. [ 37 ], and this might be a reason for its higher levels seen in MCV-positive tumors. The significance of the genes differentially expressed between the MCV-negative and positive groups is however not clear and needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

Aberrant expression of ALK and EZH2 in Merkel cell carcinoma

et al. 2017

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BackgroundDistinct characteristic features categorize Merkel cell carcinoma (MCC) into two subgroups according to the Merkel cell polyomavirus infection. Many mutational studies on MCC have been carried out in recent years without identifying a prominent driver mutation. However, there is paucity reporting the expression of cancer genes at the RNA level in MCC tumors. In this study, we studied the RNA expression profiles of 26 MCC tumors, with a goal to identify prospective molecular targets that could improve the treatment strategies of MCC.MethodsRNA expression of 50 cancer-related genes in 26 MCC tumors was analyzed by targeted amplicon based next-generation sequencing using the Ion Torrent technology and the expression compared with that of normal, non-cancerous skin samples. Sequencing data were processed using Torrent Suite™ Software. Expression profiles of MCV-negative and MCV-positive tumors were compared. Fluorescence in situ hybridization was performed to study ALK rearrangements and immunohistochemistry to study ALK expression in tumor tissue.Results ALK, CDKN2A, EZH2 and ERBB4 were overexpressed, and EGFR, ERBB2, PDGFRA and FGFR1 were underexpressed in MCC tumors compared to normal skin. In the MCV-negative tumors, MET, NOTCH1, FGFR3, and SMO were overexpressed and JAK3 and NPM1 were under-expressed compared to the MCV-positive tumors.ConclusionsHigh expression of ALK, CDKN2A and EZH2 was recorded in MCC tumors. No ALK fusion was seen by FISH analysis. Overexpression of EZH2 suggests its potential as a drug target in MCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3233-5) contains supplementary material, which is available to authorized users.

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Biophysical Characterization of Nucleophosmin Interactions with Human Immunodeficiency Virus Rev and Herpes Simplex Virus US11

Cited by 29 publications

References 80 publications

The serine-48 residue of nucleolar phosphoprotein nucleophosmin-1 plays critical role in subcellular localization and interaction with porcine circovirus type 3 capsid protein

The serine-48 residue of nucleolar phosphoprotein nucleophosmin-1 plays critical role in subcellular localization and interaction with porcine circovirus type 3 capsid protein

Nucleolar protein NPM1 is essential for circovirus replication by binding to viral capsid

Aberrant expression of ALK and EZH2 in Merkel cell carcinoma

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