RRC ID 81481
Author Xu M, Wu Z, Li W, Xue L.
Title Gp93 inhibits unfolded protein response-mediated c-Jun N-terminal kinase activation and cell invasion.
Journal J Cell Physiol
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.
Volume 239(8)
Pages e31294
Published 2024-8-1
DOI 10.1002/jcp.31294
PMID 38922869
MeSH Animals Cell Movement DNA-Binding Proteins Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster / genetics Enzyme Activation HSP90 Heat-Shock Proteins* / genetics HSP90 Heat-Shock Proteins* / metabolism Humans JNK Mitogen-Activated Protein Kinases* / metabolism Membrane Glycoproteins Neoplasm Invasiveness Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism Signal Transduction Unfolded Protein Response*
Resource
Drosophila DGRC#206596 5520R-3