Overexpression of Par-4 enhances thapsigargin-induced apoptosis via down-regulation of XIAP and inactivation of Akt in human renal cancer cells

✍ Scribed by Tae-Jin Lee; Jung-Tae Lee; Sang Hyun Kim; Yung Hyun Choi; Kyoung Seob Song; Jong-Wook Park; Taeg Kyu Kwon

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 393 KB
• Volume: 103
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21642

✦ Synopsis

Abstract

The prostate‐apoptosis‐response‐gene‐4 (Par‐4) protein has been shown to function as an effector of cell death in response to various apoptotic stimuli that trigger mitochondria and membrane receptor‐mediated cell death pathways. We found that overexpressing Par‐4 by stable transfection sensitizes Caki cells to induction of apoptosis by TRAIL and drugs that induce endoplasmic reticulum (ER) stress [thapsigargin (TG), tunicamycin (TU) and etoposide]. Ectopic expression of Par‐4 is associated with decreased levels of XIAP protein in TG‐treated cells, caused in part by XIAP protein instability and caspase activation. Levels of phospho‐Akt are decreased in Caki/Par‐4 cells to a significantly greater extent than in Caki/Vector cells by treatment with TG, and this is in turn associated with decreased levels of phospho‐PDK1, the kinase upstream of Akt. In conclusion, we provide evidence that ectopic expression of Par‐4 sensitizes Caki cells to TG and that XIAP protein instability and inactivation of Akt are important in cellular pathways affected by Par‐4. J. Cell. Biochem. 103: 358–368, 2008. © 2007 Wiley‐Liss, Inc.