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The poxvirus anaphase promoting complex regulator (PACR) promotes viral replication by manipulating the anaphase promoting complex/cyclosome (APC/C), a multisubunit ubiquitin ligase complex with essential roles in cell cycle regulation. PACR has sequence similarities to APC/C subunit 11 (APC11) and associates with APC/C subunits. However, unlike APC11, expression of PACR disrupts APC/C functions. Here, we further investigated the interaction of PACR with APC/C. Following knockdown of APC1, the subunit linking APC11/APC2 to the rest of APC/C, PACR remained bound to APC2 but not to other, distal, subunits of the complex, suggesting PACR associates with APC/C via APC2. This was supported by the demonstration, in vitro, of a direct interaction between PACR and APC2. Moreover, the presence of PACR interfered with interactions between both APC11 and APC2. Based on these observations we propose that PACR competes with APC11 for the incorporation into APC/C.

Orf virus cell cycle regulator, PACR, competes with subunit 11 of the anaphase promoting complex for incorporation into the complex