Cell-permeable peptide DEPDC1-ZNF224 interferes with transcriptional repression and oncogenicity in bladder cancer cells.
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-kappaB signaling pathway. Our findings indicate that the DEPDC1-ZNF224 complex is likely to play a critical role in bladder carcinogenesis.
Harada
Yosuke
Y
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Kanehira
Mitsugu
M
Fujisawa
Yoshiko
Y
Takata
Ryo
R
Shuin
Taro
T
Miki
Tsuneharu
T
Fujioka
Tomoaki
T
Nakamura
Yusuke
Y
Katagiri
Toyomasa
T
D000818:Animals; D019556:COS Cells; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D020690:GTPase-Activating Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D051379:Mice; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016335:Zinc Fingers / Q000235:genetics
D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; C490712:PREX2 protein, human; D012097:Repressor Proteins; C470003:ZNF224 protein, human