In summary, (i) HCMV infection downregulates Hes1 protein through IE1; (ii) IE1 directly interacts with Hes1, prompting Hes1 ubiquitination and proteasomal degradation, and thus reduces the half-life and the steady-state level of the Hes1 protein; and (iii) Sp100A is identified to be another target of HCMV IE1-mediated ubiquitination. The gene discussed is HES1; the disease is cytomegalovirus infection.