RING finger domain of ICP0 is required for MORC3 degradation. (A) Schematic diagram of ICP0 displaying internal domains and SIM-like sequences (SLS) as well as regions of mutations/deletions of the RING finger (FXE) and C-terminal (E52X) domains. NLS, nuclear localization signal. (B) HA-TetR (control) and HA-cICP0, -cICP0 FXE (Δ149-160), -cICP0 E52X (Δ594-775), -cICP0 mSLS4, and -cICP0 mSLS457 cells with the ability to express wt and mutant forms of ICP0 were treated with doxycycline (Dox) (+) or left untreated (−) and then analyzed by Western blotting. Membranes were probed with anti-MORC3 (Novus Biologicals), anti-ICP0 (11060), and anti-PML (5E10) antibodies, with anti-tubulin (Sigma-Aldrich) included as a loading control.