We next tested if the APC binding ability of pUL21a was also required for APC dissociation during infection. In this experiment, we used APC3 and APC10 as the marker for the specificity arm and cullin-ring ligase subcomplex of the APC, respectively. These two subcomplexes sit on opposite sides of the APC. APC10 has been proposed to bind APC substrates along with coactivator proteins, including Cdh1 [32] . APC10 associates with APC2 and APC11 of the ligase subcomplex, but its location in the inner cavity of the APC allows for contact with APC3 and APC6 of the specificity arm. In cells infected with ADpmUL21a PR-AA , total levels of APC3 and APC10 were similar to those in cells infected with ADpmUL21a PH-AA , allowing for a direct analysis of the efficiency of their association with the complex ( Figure 3D ). APC3 could not co-immunoprecipitate APC10 in ADpmUL21a PH-AAinfected cells, consistent with dissociation of the complex in the presence of functional pUL21a. In cells infected with ADpmU-L21a PR-AA , APC3 was able to pull down APC10 efficiently, indicating that the two subcomplexes remained associated. Finally, the integrity of the APC during ADpmUL21a PH-AA infection was largely restored upon addition of MG132, even though total protein levels were reduced likely due to MG132-induced cell death ( Figure 3D , and data not shown). These data were recapitulated during infection of wild-type and UL21a deletion viruses ( Figure S3 ). Our data provides strong evidence supporting the model that binding of pUL21a to the APC induces degradation of the APC bridge arm resulting in complex dissociation.