Triazoloacridone C-1305 impairs XBP1 splicing by acting as a potential IRE1α endoribonuclease inhibitor - Publikacja - MOST Wiedzy

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Triazoloacridone C-1305 impairs XBP1 splicing by acting as a potential IRE1α endoribonuclease inhibitor

Abstrakt

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.

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Kategoria:
Publikacja w czasopiśmie
Typ:
artykuły w czasopismach
Opublikowano w:
CELLULAR & MOLECULAR BIOLOGY LETTERS nr 26, strony 1 - 17,
ISSN: 1425-8153
Język:
angielski
Rok wydania:
2021
Opis bibliograficzny:
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:
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1186/s11658-021-00255-y
Źródła finansowania:
Weryfikacja:
Politechnika Gdańska

wyświetlono 81 razy

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