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Human Cytomegalovirus Inactivates the G0/G1-APC/C Ubiquitin Ligase by Cdh1 Dissociation
Lüder Wiebusch, Miriam Bach, Ralf Uecker and Christian Hagemeier
volume 4 | issue 10
october 2005Pages: 1435 - 1439
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The anaphase promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that targets regulators of the cell division cycle for degradation by the 26S proteasome. Discovered as a key regulator of mitosis, the APC/C has more recently been recognized to also play a limiting role in the control of G0 maintenance, G1/S-transition and DNA-replication. Human cytomegalovirus (HCMV) has been shown to interfere with cell cycle regulation at different levels. It can induce an S phase-prone proliferation program in quiescent cells but at the same time this virus directly inhibits competitive cellular DNA replication. Here we show, that human cytomegalovirus (HCMV) inactivates the G0/G1 APC/C rapidly after infection of quiescent fibroblasts, resulting in the untimely stabilisation of APC/C substrates. APC/C inactivation is caused by the dissociation of its positive regulator, Cdh1. Surprisingly, this dissociation is independent from known Cdh1 inhibitors, Emi1 and Cyclin A, suggesting that APC/C-Cdh1 inhibition by HCMV is directly caused by a viral protein or an intermediate cellular factor distinct from Emi1 and Cyclin A. Thus, upon infection of quiescent cells HCMV not only activates the E2F-dependent G1/S transcription program but also facilitates protein accumulation of APC/C substrates by rapid Cdh1 dissociation.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.