Supplementary Figure Legends 1-10 from Cell-Permeable Peptide DEPDC1-ZNF224 Interferes with Transcriptional Repression and Oncogenicity in Bladder Cancer Cells
ARTICLE ABSTRACT
Bladder cancer is the second most common genitourinary cancer worldwide, yet its oncogenic origins remain poorly understood. The cancer-testis antigen DEPDC1 was shown recently to contribute to bladder cancer oncogenesis. In this study, we examined the biological functions of DEPDC1 and defined a potential therapeutic strategy to target this molecule. Coimmunoprecipitation and immunocytochemistry revealed that DEPDC1 interacted and colocalized with zinc finger transcription factor ZNF224, a known transcriptional repressor. Inhibiting this interaction with a cell-permeable peptide corresponding to the ZNF224-interacting domain in DEPDC1 induced apoptosis of bladder cancer cells in vitro and in vivo. By inhibiting DEPDC1-ZNF224 complex formation, this peptide triggered transcriptional activation of A20, a potent inhibitor of the NF-κB signaling pathway. Our findings indicate that the DEPDC1-ZNF224 complex is likely to play a critical role in bladder carcinogenesis. Cancer Res; 70(14); 5829–39. ©2010 AACR.