期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：46
页码：19527-19532
DOI：10.1073/pnas.0905893106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The anaphase-promoting complex (APC), or cyclosome, is a ubiquitin ligase with major roles in cell cycle regulation. It is required for mitotic exit, but must be deactivated for the G1/S phase transition to occur. APC consists of at least 12 subunits with the catalytic core formed by a scaffold protein, APC2, and a RING-H2 protein, APC11. APC11 facilitates ubiquitin chain formation by recruiting ubiquitin-charged conjugating enzymes through its RING-H2 domain. We report that a small number of poxviruses encode RING-H2 proteins with sequence similarities to APC11. We show that a representative of these viral proteins mimics APC11 in its interactions with APC, but unlike APC11, the viral protein fails to promote ubiquitin chain formation. This absence of ubiquitin ligase activity is linked to a distinctive sequence variation within its RING-H2 domain. Expression of the viral protein led to cell cycle deregulation and the accumulation of APC substrates in a manner consistent with impaired APC function. Our data characterize this protein as a regulator of APC activity, and consequently, we have called it PACR (poxvirus APC/cyclosome regulator). Deletion of the PACR gene substantially reduced viral replication. Here, we report a viral mimic of an APC component and reveal an intriguing mechanism by which viruses can manipulate cell cycle progression and, thereby, promote their own replication.
