In:
Journal of Cellular Biochemistry, Wiley, Vol. 113, No. 12 ( 2012-12), p. 3692-3700
Abstract:
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 cFLIP L protein levels together with a concomitant increase in the CHOP protein. Interestingly, Wit A down‐regulated cFLIP L 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 cFLIP L protein expression but did not alter cFLIP L mRNA levels. Additionally, we observed that siRNA‐mediated CHOP silencing recovered the cFLIP L expression decreased by CHOP‐inducing agents in Caki cells. Finally, we showed that CHOP facilitates ubiquitin/proteasome‐mediated cFLIP L degradation, leading to down‐regulation of cFLIP L . Finally, cFLIP L over‐expression reduced cell death induced by treatment with brefeldin A, thapsigargin, and silybin. Taken together, our results provide novel evidence that cFLIP L is a CHOP control target and that CHOP‐induced down‐regulation of cFLIP L is due to activation of the ubiquitin/proteasome pathways. J. Cell. Biochem. 113: 3692–3700, 2012. © 2012 Wiley Periodicals, Inc.
Type of Medium:
Online Resource
ISSN:
0730-2312
,
1097-4644
Language:
English
Publisher:
Wiley
Publication Date:
2012
detail.hit.zdb_id:
1479976-5
SSG:
12
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