Insight into the mechanism of pUL21a-mediated APC regulation may also have broad impact on cancer and neuronal disease. Due to its essential role in cell cycle progression, the APC is a promising target for novel anti-cancer therapeutics [16, 43] . In fact, we found in this study that overexpression of pUL21a essentially prevented the proliferation of a transformed cell line ( Figure S7 ), suggesting that pUL21a regulation of the APC could inhibit cancer cell growth. Furthermore, several recent studies have also highlighted a vital role of the APC in neuronal development (for a review, see [44] ). HCMV infects neuronal cells and congenital HCMV infection leads to neuronal disease and severe complications such as blindness, hearing loss, and mental retardation. It is reasonable to speculate that inhibition of the APC by pUL21a may play a role in promoting neuronal disease in congenitally infected infants. Therefore, an understanding of pUL21a-APC interaction may reveal novel mechanisms of APC assembly and regulation, give further impetus to target the APC for anti-cancer therapies, and uncover new insights into the molecular basis of HCMV pathogenesis.