Binding and nuclear relocalization of protein kinase R by human cytomegalovirus TRS1.

Binding and nuclear relocalization of protein kinase R by human cytomegalovirus TRS1. Research Abstract Details 

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Binding and nuclear relocalization of protein kinase R by human cytomegalovirus TRS1. Abstract Text:

Morgan Hakki,Emily E Marshall,Katherine L De Niro,Adam P Geballe,

The human cytomegalovirus (HCMV) TRS1 and IRS1 genes block the phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2alpha) and the consequent shutoff of cellular protein synthesis that occur during infection with vaccinia virus (VV) deleted of the double-stranded RNA binding protein gene E3L (VVDeltaE3L). To further define the underlying mechanism, we first evaluated the effect of pTRS1 on protein kinase R (PKR), the double-stranded RNA (dsRNA)-dependent eIF2alpha kinase. Immunoblot analyses revealed that pTRS1 expression in the context of a VVDeltaE3L recombinant decreased levels of PKR in the cytoplasm and increased its levels in the nucleus of infected cells, an effect not seen with wild-type VV or a VVDeltaE3L recombinant virus expressing E3L. This effect of pTRS1 was confirmed by visualizing the nuclear relocalization of PKR-EGFP expressed by transient transfection. PKR present in both the nuclear and cytoplasmic fractions was nonphosphorylated, indicating that it was unactivated when TRS1 was present. PKR also accumulated in the nucleus during HCMV infection as determined by indirect immunofluorescence and immunoblot analysis. Binding assays revealed that pTRS1 interacted with PKR in mammalian cells and in vitro. This interaction required the same carboxy-terminal region of pTRS1 that is necessary to rescue VVDeltaE3L replication in HeLa cells. The carboxy terminus of pIRS1 was also required for rescue of VVDeltaE3L and for mediating an interaction of pIRS1 with PKR. These results suggest that these HCMV genes directly interact with PKR and inhibit its activation by sequestering it in the nucleus, away from both its activator, cytoplasmic dsRNA, and its substrate, eIF2alpha.

Binding and nuclear relocalization of protein kinase R by human cytomegalovirus TRS1. Publishing Authors By Initials

M Hakki,EE Marshall,KL De Niro,AP Geballe,

For similar proteins: viral proteins research abstracts see: proteins: viral proteins research

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Binding and nuclear relocalization of protein kinase R by human cytomegalovirus TRS1. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of virology

VOLUME: 80

Page Numbers: 11817-26

Journal Abbreviation: J. Virol.

ISSN: 0022-538X

DAY: 20

MONTH: 09

YEAR: 2006

Binding and nuclear relocalization of protein kinase R by human cytomegalovirus TRS1. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 113724

Binding and nuclear relocalization of protein kinase R by human cytomegalovirus TRS1. Keywords Mesh Terms:

KEYWORDS: Viral Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: Binding and nuclear relocalization of protein kinase R by human cytomegalovirus TRS1. Information

Substance Name: Protein Kinases

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Binding and nuclear relocalization of protein kinase R by human cytomegalovirus TRS1.

AFFILIATION: Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109, USA.

Country: United States

AGENCY: United States NCI

GRANT: T32 CA 09229

ACRONYM: CA

MEDLINETA: J Virol

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