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Title: Sites and roles of phosphorylation of the human cytomegalovirus DNA polymerase subunit UL44

Abstract

The human cytomegalovirus DNA polymerase subunit UL44 is a phosphoprotein, but its sites and roles of phosphorylation have not been investigated. We compared sites of phosphorylation of UL44 in vitro by the viral protein kinase UL97 and cyclin-dependent kinase 1 with those in infected cells. Transient treatment of infected cells with a UL97 inhibitor greatly reduced labeling of two minor UL44 phosphopeptides. Viruses containing alanine substitutions of most UL44 residues that are phosphorylated in infected cells exhibited at most modest effects on viral DNA synthesis and yield. However, substitution of highly phosphorylated sites adjacent to the nuclear localization signal abolished viral replication. The results taken together are consistent with UL44 being phosphorylated directly by UL97 during infection, and a crucial role for phosphorylation-mediated nuclear localization of UL44 for viral replication, but lend little support to the widely held hypothesis that UL97-mediated phosphorylation of UL44 is crucial for viral DNA synthesis.

Authors:
; ; ; ;
Publication Date:
OSTI Identifier:
21587884
Resource Type:
Journal Article
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 417; Journal Issue: 2; Other Information: DOI: 10.1016/j.virol.2011.06.008; PII: S0042-6822(11)00272-8; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0042-6822
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; DNA; HUMAN POPULATIONS; HYPOTHESIS; IN VITRO; PHOSPHOPROTEINS; PHOSPHORYLATION; SYNTHESIS; CHEMICAL REACTIONS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; POPULATIONS; PROTEINS

Citation Formats

Silva, Laurie A., Strang, Blair L., Lin, Eric W., Kamil, Jeremy P., and Coen, Donald M., E-mail: don_coen@hms.harvard.edu. Sites and roles of phosphorylation of the human cytomegalovirus DNA polymerase subunit UL44. United States: N. p., 2011. Web. doi:10.1016/j.virol.2011.06.008.
Silva, Laurie A., Strang, Blair L., Lin, Eric W., Kamil, Jeremy P., & Coen, Donald M., E-mail: don_coen@hms.harvard.edu. Sites and roles of phosphorylation of the human cytomegalovirus DNA polymerase subunit UL44. United States. doi:10.1016/j.virol.2011.06.008.
Silva, Laurie A., Strang, Blair L., Lin, Eric W., Kamil, Jeremy P., and Coen, Donald M., E-mail: don_coen@hms.harvard.edu. Thu . "Sites and roles of phosphorylation of the human cytomegalovirus DNA polymerase subunit UL44". United States. doi:10.1016/j.virol.2011.06.008.
@article{osti_21587884,
title = {Sites and roles of phosphorylation of the human cytomegalovirus DNA polymerase subunit UL44},
author = {Silva, Laurie A. and Strang, Blair L. and Lin, Eric W. and Kamil, Jeremy P. and Coen, Donald M., E-mail: don_coen@hms.harvard.edu},
abstractNote = {The human cytomegalovirus DNA polymerase subunit UL44 is a phosphoprotein, but its sites and roles of phosphorylation have not been investigated. We compared sites of phosphorylation of UL44 in vitro by the viral protein kinase UL97 and cyclin-dependent kinase 1 with those in infected cells. Transient treatment of infected cells with a UL97 inhibitor greatly reduced labeling of two minor UL44 phosphopeptides. Viruses containing alanine substitutions of most UL44 residues that are phosphorylated in infected cells exhibited at most modest effects on viral DNA synthesis and yield. However, substitution of highly phosphorylated sites adjacent to the nuclear localization signal abolished viral replication. The results taken together are consistent with UL44 being phosphorylated directly by UL97 during infection, and a crucial role for phosphorylation-mediated nuclear localization of UL44 for viral replication, but lend little support to the widely held hypothesis that UL97-mediated phosphorylation of UL44 is crucial for viral DNA synthesis.},
doi = {10.1016/j.virol.2011.06.008},
journal = {Virology},
issn = {0042-6822},
number = 2,
volume = 417,
place = {United States},
year = {2011},
month = {9}
}