Abstract:
:Infection of quiescent cells by human cytomegalovirus (HCMV) elicits severe cell cycle deregulation, resulting in a G(1)/S arrest, which can be partly attributed to the inactivation of the anaphase-promoting complex (APC). As we previously reported, the premature phosphorylation of its coactivator Cdh1 and/or the dissociation of the core complex can account for the inactivation. We have expanded on these results and further delineated the key components required for disabling the APC during HCMV infection. The viral protein kinase UL97 was hypothesized to phosphorylate Cdh1, and consistent with this, phosphatase assays utilizing a virus with a UL97 deletion mutation (ΔUL97 virus) indicated that Cdh1 is hypophosphorylated at early times in the infection. Mass spectrometry analysis demonstrated that UL97 can phosphorylate Cdh1 in vitro, and the majority of the sites identified correlated with previously characterized cyclin-dependent kinase (Cdk) consensus sites. Analysis of the APC core complex during ΔUL97 virus infection showed APC dissociation occurring at the same time as during infection with wild-type virus, suggesting that the UL97-mediated phosphorylation of Cdh1 is not required for this to occur. Further investigation of the APC subunits showed a proteasome-dependent loss of the APC5 and APC4 subunits that was temporally associated with the disassembly of the APC. Immediate early viral gene expression was not sufficient for the degradation of APC4 and APC5, indicating that a viral early gene product(s), possibly in association with a de novo-synthesized cellular protein(s), is involved.
journal_name
J Viroljournal_title
Journal of virologyauthors
Tran K,Kamil JP,Coen DM,Spector DHdoi
10.1128/JVI.01260-10subject
Has Abstractpub_date
2010-10-01 00:00:00pages
10832-43issue
20eissn
0022-538Xissn
1098-5514pii
JVI.01260-10journal_volume
84pub_type
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journal_title:Journal of virology
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1128/JVI.52.1.55-62.1984
更新日期:1984-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.05013-11
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
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journal_title:Journal of virology
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2003-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2019-04-03 00:00:00
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pub_type: 杂志文章
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更新日期:2008-03-01 00:00:00