CHOP down-regulates cFLIPL expression by promoting ubiquitin/proteasome-mediated cFLIPL degradation
- CHOP down-regulates cFLIPL expression by promoting ubiquitin/proteasome-mediated cFLIPL degradation
- 이태진; 노효정; 이성준; 성언기; 송인환; 김주영; 우창훈; 권택규[권택규]
- ENDOPLASMIC-RETICULUM STRESS; TRAIL-INDUCED APOPTOSIS; DEATH RECEPTOR 5; KAPPA-B SIGNALS; CELL-DEATH; C-FLIP; HOMOLOGOUS PROTEIN; PROSTATE-CANCER; BINDING-PROTEIN; ACTIVATION
- Issue Date
- JOURNAL OF CELLULAR BIOCHEMISTRY, v.113, no.12, pp.3692 - 3700
- The transcription factor CHOP/GADD153 is induced during the unfolded protein response and is related to the induction of ER stress-mediated apoptosis. However, how CHOP is organized between the pro-survival and pro-apoptotic roles of ER stress remains largely undefined. In this study, we identified the apoptosis regulating protein suppressed by CHOP. We found that treatment of Caki cells with CHOP-inducing drugs including withaferin A, thapsigargin, brefeldin A, and silybin led to a strong reduction in cFLIPL protein levels together with a concomitant increase in the CHOP protein. Interestingly, Wit A down-regulated cFLIPL expression via both suppressing mRNA transcription and increasing cFLIPL protein instability. We also found that forced expression of CHOP dose-dependently led to a decrease of cFLIPL protein expression but did not alter cFLIPL mRNA levels. Additionally, we observed that siRNA-mediated CHOP silencing recovered the cFLIPL expression decreased by CHOP-inducing agents in Caki cells. Finally, we showed that CHOP facilitates ubiquitin/proteasome-mediated cFLIPL degradation, leading to down-regulation of cFLIPL. Finally, cFLIPL over-expression reduced cell death induced by treatment with brefeldin A, thapsigargin, and silybin. Taken together, our results provide novel evidence that cFLIPL is a CHOP control target and that CHOP-induced down-regulation of cFLIPL is due to activation of the ubiquitin/proteasome pathways. J. Cell. Biochem. 113: 36923700, 2012. (C) 2012 Wiley Periodicals, Inc.
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