title: Association of human cytomegalovirus proteins IRS1 and TRS1 with the viral DNA polymerase accessory subunit UL44.
abstract: Multiple proteins interacting with DNA polymerases orchestrate DNA replication. Human cytomegalovirus (HCMV) encodes a DNA polymerase that includes the presumptive processivity factor UL44. UL44 is structurally homologous to the eukaryotic DNA polymerase processivity factor proliferating cell nuclear antigen (PCNA), which interacts with numerous proteins. Previous proteomic analysis has identified the HCMV protein IRS1 as a candidate protein interacting with UL44. Nuclease-resistant reciprocal co-immunoprecipitation of UL44 with IRS1 and with TRS1, which has an amino terminus identical to that of IRS1, was observed from lysate of cells infected with viruses expressing epitope-tagged UL44, epitope-tagged IRS1 or epitope-tagged TRS1. Western blotting of protein immunoprecipitated from infected cell lysate indicated that epitope-tagged IRS1 and TRS1 do not associate simultaneously with UL44. Glutathione S-transferase pull-down experiments indicated that IRS1 and TRS1 interact with UL44 via a region that is identical in both proteins. Taken together, these data suggest that IRS1 and TRS1 may compete for association with UL44 and may affect UL44 function differentially.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Blair L
authors.initials: BL
authors.lastname: Strang
authors.forename: Adam P
authors.initials: AP
authors.lastname: Geballe
authors.forename: Donald M
authors.initials: DM
authors.lastname: Coen
mesh_terms: D001667:Binding, Competitive; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016679:Genome, Viral; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009842:Oligopeptides; D010455:Peptides / Q000235:genetics; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C072217:ICP36 protein, Cytomegalovirus; D009842:Oligopeptides; D010455:Peptides; D011994:Recombinant Proteins; C072216:TRS1 protein, Human herpesvirus 5; D014764:Viral Proteins; C085706:FLAG peptide; D005982:Glutathione Transferase
references.citation: J Virol. 2005 Jun;79(12):7311-8
references.pmid: 15919885
references.citation: J Virol. 2009 May;83(9):4112-20
references.pmid: 19211736
references.citation: J Virol. 2008 Feb;82(4):1638-46
references.pmid: 18057245
references.citation: J Virol. 2007 Oct;81(19):10659-68
references.pmid: 17634236
references.citation: Virology. 1997 Mar 31;230(1):22-34
references.pmid: 9126259
references.citation: J Mol Biol. 2008 Aug 29;381(2):276-88
references.pmid: 18599070
references.citation: J Virol. 2002 Dec;76(23):12290-9
references.pmid: 12414969
references.citation: J Virol. 1993 Dec;67(12):6979-88
references.pmid: 8230421
references.citation: J Virol. 1997 Feb;71(2):1485-96
references.pmid: 8995674
references.citation: J Virol. 2006 Dec;80(23):11817-26
references.pmid: 16987971
references.citation: Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6958-62
references.pmid: 1495986
references.citation: J Virol. 2000 Sep;74(17):7720-9
references.pmid: 10933677
references.citation: J Virol. 1997 Jun;71(6):4400-8
references.pmid: 9151830
references.citation: J Virol. 2004 Jun;78(11):5856-66
references.pmid: 15140983
references.citation: J Virol. 1996 Aug;70(8):5131-42
references.pmid: 8764021
references.citation: J Virol. 2004 Sep;78(17):9084-92
references.pmid: 15308704
references.citation: Biotechniques. 2006 Feb;40(2):191-7
references.pmid: 16526409
references.citation: J Virol. 1992 Jul;66(7):4126-33
references.pmid: 1318399
references.citation: J Virol. 2004 Jan;78(1):158-67
references.pmid: 14671097
references.citation: J Virol. 1993 May;67(5):2575-82
references.pmid: 8386266
references.citation: J Virol. 2008 Jan;82(1):96-104
references.pmid: 17959680
references.citation: J Virol. 2005 Oct;79(19):12487-94
references.pmid: 16160176
references.citation: J Virol. 2007 Jun;81(12):6197-206
references.pmid: 17409154
references.citation: J Virol. 2004 Jan;78(1):197-205
references.pmid: 14671101
references.citation: J Virol. 2010 Feb;84(4):1771-84
references.pmid: 20007282
references.citation: Virol J. 2005 Jul 15;2:55
references.pmid: 16022730
references.citation: J Cell Sci. 2003 Aug 1;116(Pt 15):3051-60
references.pmid: 12829735
references.citation: J Biol Chem. 2006 Feb 24;281(8):5224-32
references.pmid: 16371349
references.citation: J Virol. 1992 Feb;66(2):1050-8
references.pmid: 1370547
references.citation: J Virol. 2009 Aug;83(15):7581-9
references.pmid: 19457994
references.citation: J Virol. 1996 Jan;70(1):373-82
references.pmid: 8523551
references.citation: Mol Cell. 2004 Jul 23;15(2):233-44
references.pmid: 15260974
references.citation: J Virol. 1996 Nov;70(11):7398-413
references.pmid: 8892858
references.citation: Cell. 2007 May 18;129(4):665-79
references.pmid: 17512402