Search
Triazoloacridone C-1305 impairs XBP1 splicing by acting as a potential IRE1α endoribonuclease inhibitor
Abstract
Inositol requiring enzyme 1 alpha (IRE1α) is one of three signaling sensors in the unfolding protein response (UPR) that alleviates endoplasmic reticulum (ER) stress in cells and functions to promote cell survival. During conditions of irrevocable stress, proapoptotic gene expression is induced to promote cell death. One of the three signaling stressors, IRE1α is an serine/threonine-protein kinase/endoribonuclease (RNase) that promotes nonconventional splicing of XBP1 mRNA that is translated to spliced XBP1 (XBP1s), an active prosurvival transcription factor. Interestingly, elevated IRE1α and XBP1s are both associated with poor cancer survival and drug resistance. In this study, we used next-generation sequencing analyses to demonstrate that triazoloacridone C-1305, a microtubule stabilizing agent that also has topoisomerase II inhibitory activity, dramatically decreases XBP1s mRNA levels and protein production during ER stress conditions, suggesting that C-1305 does this by decreasing IRE1α’s endonuclease activity.
Citations
-
1 0
CrossRef
-
0
Web of Science
-
9
Scopus
Authors (7)
-
Sylwia Bartoszewska
-
Jarosław Króliczewski
-
David Crossman
-
Aneta Pogorzelska
-
James F. Collawn
-
Rafal Bartoszewski
Cite as
Full text
- Publication version
- Accepted or Published Version
- License
-
open in new tab
Keywords
Details
- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
-
CELLULAR & MOLECULAR BIOLOGY LETTERS
no. 26,
pages 1 - 17,
ISSN: 1425-8153 - Language:
- English
- Publication year:
- 2021
- Bibliographic description:
- Bartoszewska S., Króliczewski J., Crossman D., Pogorzelska A., Bagiński M., Collawn J. F., Bartoszewski R.: Triazoloacridone C-1305 impairs XBP1 splicing by acting as a potential IRE1α endoribonuclease inhibitor// CELLULAR & MOLECULAR BIOLOGY LETTERS -Vol. 26,iss. 1 (2021), s.1-17
- DOI:
- Digital Object Identifier (open in new tab) 10.1186/s11658-021-00255-y
- Sources of funding:
- Verified by:
- Gdańsk University of Technology
seen 122 times
Recommended for you
The Unfolded Protein Response: A Double-Edged Sword for Brain Health
- M. Gebert,
- J. Sławski,
- L. Kalinowski
- + 2 authors
Metabolic transformation of antitumor acridinone C-1305 but not C-1311 via selective cellular expression of UGT1A10 increases cytotoxic response: implications for clinical use.
- M. Pawłowska,
- R. Chu,
- B. Fedejko-Kap
- + 4 authors