2015
DOI: 10.1530/erc-15-0019
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Improvement of chemotherapeutic drug efficacy by endoplasmic reticulum stress

Abstract: Tunicamycin (TUN), an inhibitor of protein glycosylation and therefore a potent stimulator of endoplasmic reticulum (ER) stress, has been used to improve anticancer drug efficacy, but the underlying mechanism remains obscure. In this study, we show that acute administration of TUN in mice induces the unfolded protein response and suppresses the levels of P21, a cell cycle regulator with anti-apoptotic activity. The inhibition of P21 after ER stress appears to be C/EBP homologous protein (CHOP)-dependent becaus… Show more

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Cited by 36 publications
(41 citation statements)
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“…Elucidation of the shift toward the pro-apoptotic function of the UPR promises application in the management of various ER stress-associated conditions such as diabetes and neurodegeneration. Other and our labs recently demonstrated the pivotal role of p21 in this process by mechanisms involving inhibition of p21 expression during the advanced stages of ER stress (23,24,26,28). Consistent with these findings, p21 suppression is permissive for the induction of ER stressrelated apoptosis, as it decreases the apoptotic cut-off of cells undergoing ER stress (27).…”
Section: Introductionsupporting
confidence: 77%
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“…Elucidation of the shift toward the pro-apoptotic function of the UPR promises application in the management of various ER stress-associated conditions such as diabetes and neurodegeneration. Other and our labs recently demonstrated the pivotal role of p21 in this process by mechanisms involving inhibition of p21 expression during the advanced stages of ER stress (23,24,26,28). Consistent with these findings, p21 suppression is permissive for the induction of ER stressrelated apoptosis, as it decreases the apoptotic cut-off of cells undergoing ER stress (27).…”
Section: Introductionsupporting
confidence: 77%
“…To see this illustration in color, the reader is referred to the web version of this article at www.liebert pub.com/ars activation is induced. The fact that p21 ablation was insufficient to abrogate the increased sensitivity of the aged islets to high glucose and tunicamycin (aged p21KO islets remained more sensitive than younger islets), despite that it is regulated by CHOP (23,24), suggests that CHOP attains these aging-associated effects by p21-independent mechanisms. To that end, although CHOP's activity is instructive for ER stress-associated apoptosis, for p21 such activity is rather permissive.…”
Section: Discussionmentioning
confidence: 99%
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