Abstract:
In eukaryotes, Hsp90B1 serves as a vital chaperonin, facilitating the accurate folding of proteins. Interestingly, Hsp90B1 exhibits contrasting roles in the development of various types of cancers, although the underlying reasons for this duality remain enigmatic. Through the utilization of the Drosophila model, this study unveils the functional significance of Gp93, the Drosophila ortholog of Hsp90B1, which hitherto had limited reported developmental functions. Employing the Drosophila cell invasion model, we elucidated the pivotal role of Gp93 in regulating cell invasion and modulating c-Jun N-terminal kinase (JNK) activation. Furthermore, our investigation highlights the involvement of the unfolded protein response-associated IRE1/XBP1 pathway in governing Gp93 depletion-induced, JNK-dependent cell invasion. Collectively, these findings not only uncover a novel molecular function of Gp93 in Drosophila, but also underscore a significant consideration pertaining to the testing of Hsp90B1 inhibitors in cancer therapy.
摘要:
在真核生物中,Hsp90B1是一种重要的伴侣,促进蛋白质的准确折叠。有趣的是,Hsp90B1在各种类型的癌症的发展中表现出不同的作用,尽管这种双重性的根本原因仍然是神秘的。通过利用果蝇模型,这项研究揭示了Gp93的功能意义,Gp93是Hsp90B1的果蝇直系同源物,迄今报道的发育功能有限。采用果蝇细胞侵袭模型,我们阐明了Gp93在调节细胞侵袭和调节c-JunN末端激酶(JNK)激活中的关键作用。此外,我们的研究强调了与未折叠蛋白反应相关的IRE1/XBP1通路在控制Gp93耗竭诱导的过程中的参与,JNK依赖性细胞侵袭。总的来说,这些发现不仅揭示了果蝇中Gp93的新分子功能,但也强调了与癌症治疗中Hsp90B1抑制剂的测试有关的重要考虑。