Overall, our results show that cDOPEY2 acts as a scaffold to facilitate the ubiquitination and degradation of CPEB4 in a TRIM25-dependent manner, thereby boosting cisplatin-induced apoptosis by suppressing CPEB4-promoted Mcl-1 translation and alleviating cisplatin resistance in ESCC cells (Fig. 8). This evidence concerns the gene CPEB4 and esophageal squamous cell carcinoma.