Proteasome Down-regulation is Partly Mediated by Slug/Snail2 in Hepatocarcinoma Cells

Snail family proteins (Snail1 and Slug/Snail2) are transcription factors that regulate transcription of molecules during epithelial-mesenchymal transition (EMT). Snail1/2 is known to bind to the E-box motif (CANNTG). The proteasome activity is decreased in EMT (Kim et al., 2011), and several E-box motifs are found in the promoters of genes coding for proteasome subunits. We used a new protein-binding microarray to specify the Slug/Snail2 binding sequence. Among 563 9-mer clusters, the motif CACCTGC yielded the highest P-value in the Wilcoxon-Mann-Whitney test. Within this motif, the A and T were absolutely required, and CC was preferred, but could be replaced by GG with little effect. In hepatocytes overexpressing Slug/Snail2, the 20S proteasome expression and proteasome activity were decreased partly due to the down-regulation of proteasome subunit beta type 2 (PSMB2) and PSMB3 transcription.