Triazoloacridone C-1305 impairs XBP1 splicing by acting as a potential IRE1α endoribonuclease inhibitor
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چکیده
منابع مشابه
Identification of Doxorubicin as an Inhibitor of the IRE1α-XBP1 Axis of the Unfolded Protein Response
Activation of the IRE1α-XBP1 branch of the unfolded protein response (UPR) has been implicated in multiple types of human cancers, including multiple myeloma (MM). Through an in silico drug discovery approach based on protein-compound virtual docking, we identified the anthracycline antibiotic doxorubicin as an in vitro and in vivo inhibitor of XBP1 activation, a previously unknown activity for...
متن کاملThe antitumor triazoloacridone C-1305 is a topoisomerase II poison with unusual properties.
C-1305 [S-[[3-(dimethylamino)propyl]amino]-8-hydroxy-6H-v-triazolo[4,5,1-de]acridin-6-one] is a triazoloacridone with excellent activity in colon cancer models. The mechanism of C-1305 is unknown, although similarities in the chemical structure between C-1305 and amsacrine suggest common cellular targets. Here, we report that C-1305 is a topoisomerase II poison that is able to induce cleavable ...
متن کاملInduction of unique structural changes in guanine-rich DNA regions by the triazoloacridone C-1305, a topoisomerase II inhibitor with antitumor activities
We recently reported that the antitumor triazoloacridone, compound C-1305, is a topoisomerase II poison with unusual properties. In this study we characterize the DNA interactions of C-1305 in vitro, in comparison with other topoisomerase II inhibitors. Our results show that C-1305 binds to DNA by intercalation and possesses higher affinity for GC- than AT-DNA as revealed by surface plasmon res...
متن کاملInhibition of IRE1α-mediated XBP1 mRNA cleavage by XBP1 reveals a novel regulatory process during the unfolded protein response
Background: The mammalian endoplasmic reticulum (ER) continuously adapts to the cellular secretory load by the activation of an unfolded protein response (UPR). This stress response results in expansion of the ER, upregulation of proteins involved in protein folding and degradation, and attenuation of protein synthesis. The response is orchestrated by three signalling pathways each activated ...
متن کاملLong-Range Inhibitor-Induced Conformational Regulation of Human IRE1α Endoribonuclease Activity.
Activation of the inositol-requiring enzyme-1 alpha (IRE1α) protein caused by endoplasmic reticulum stress results in the homodimerization of the N-terminal endoplasmic reticulum luminal domains, autophosphorylation of the cytoplasmic kinase domains, and conformational changes to the cytoplasmic endoribonuclease (RNase) domains, which render them functional and can lead to the splicing of X-box...
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ژورنال
عنوان ژورنال: Cellular & Molecular Biology Letters
سال: 2021
ISSN: 1425-8153,1689-1392
DOI: 10.1186/s11658-021-00255-y