Association of human cytomegalovirus proteins IRS1 and TRS1 with the viral DNA polymerase accessory subunit UL44.
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.
Strang
Blair L
BL
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Geballe
Adam P
AP
Coen
Donald M
DM
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*
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
J Virol. 2005 Jun;79(12):7311-8
15919885
J Virol. 2009 May;83(9):4112-20
19211736
J Virol. 2008 Feb;82(4):1638-46
18057245
J Virol. 2007 Oct;81(19):10659-68
17634236
Virology. 1997 Mar 31;230(1):22-34
9126259
J Mol Biol. 2008 Aug 29;381(2):276-88
18599070
J Virol. 2002 Dec;76(23):12290-9
12414969
J Virol. 1993 Dec;67(12):6979-88
8230421
J Virol. 1997 Feb;71(2):1485-96
8995674
J Virol. 2006 Dec;80(23):11817-26
16987971
Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6958-62
1495986
J Virol. 2000 Sep;74(17):7720-9
10933677
J Virol. 1997 Jun;71(6):4400-8
9151830
J Virol. 2004 Jun;78(11):5856-66
15140983
J Virol. 1996 Aug;70(8):5131-42
8764021
J Virol. 2004 Sep;78(17):9084-92
15308704
Biotechniques. 2006 Feb;40(2):191-7
16526409
J Virol. 1992 Jul;66(7):4126-33
1318399
J Virol. 2004 Jan;78(1):158-67
14671097
J Virol. 1993 May;67(5):2575-82
8386266
J Virol. 2008 Jan;82(1):96-104
17959680
J Virol. 2005 Oct;79(19):12487-94
16160176
J Virol. 2007 Jun;81(12):6197-206
17409154
J Virol. 2004 Jan;78(1):197-205
14671101
J Virol. 2010 Feb;84(4):1771-84
20007282
Virol J. 2005 Jul 15;2:55
16022730
J Cell Sci. 2003 Aug 1;116(Pt 15):3051-60
12829735
J Biol Chem. 2006 Feb 24;281(8):5224-32
16371349
J Virol. 1992 Feb;66(2):1050-8
1370547
J Virol. 2009 Aug;83(15):7581-9
19457994
J Virol. 1996 Jan;70(1):373-82
8523551
Mol Cell. 2004 Jul 23;15(2):233-44
15260974
J Virol. 1996 Nov;70(11):7398-413
8892858
Cell. 2007 May 18;129(4):665-79
17512402