Here we experimentally demonstrated that the CDC20 promoter hotspot mutations disrupt the binding of transcriptional repressor ELK4, and consequently up-regulate the transcription of CDC20. CDC20 is known to have cancer-driving function through the regulation of cell cycle progression, and consistently CDC20 expression is ubiquitously up-regulated in various cancer types (Chang et al., 2012; Gayyed et al., 2016; Kim et al., 2014; Wang et al., 2013) (Figure 3A). This evidence concerns the gene ELK4 and cancer.