E6AP/UBE3A catalyzes encephalomyocarditis virus 3C protease polyubiquitylation and promotes its concentration reduction in virus-infected cells.

The encephalomyocarditis virus (EMCV) 3C protease (3C) is one of a small number of viral proteins whose concentration is known to be regulated by the cellular ubiquitin-proteasome system. Here we report that the ubiquitin-conjugating enzyme UbcH7/UBE2L3 and the ubiquitin-protein ligase E6AP/UBE3A are components of a previously unknown EMCV 3C-polyubiquitylating pathway. Following the identification of UbcH7/UBE2L3 as a participant in 3C ubiquitylation, we purified a UbcH7-dependent 3C-ubiquitylating activity from mouse cells, which we identified as E6AP.