G alpha(12/13) inhibition enhances the anticancer effect of bortezomib through PSMB5 downregulation
DC Field | Value | Language |
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dc.contributor.author | Yang, Yoon Mee | - |
dc.contributor.author | Lee, Sanghwan | - |
dc.contributor.author | Nam, Chang Won | - |
dc.contributor.author | Ha, Ji Hee | - |
dc.contributor.author | Jayaraman, Muralidharan | - |
dc.contributor.author | Dhanasekaran, Danny N. | - |
dc.contributor.author | Lee, Chang Ho | - |
dc.contributor.author | Kwak, Mi-Kyoung | - |
dc.contributor.author | Kim, Sang Geon | - |
dc.date.accessioned | 2022-12-20T16:33:37Z | - |
dc.date.available | 2022-12-20T16:33:37Z | - |
dc.date.created | 2022-08-27 | - |
dc.date.issued | 2010-07 | - |
dc.identifier.issn | 0143-3334 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/174501 | - |
dc.description.abstract | Bortezomib is a proteasome inhibitor approved for anticancer therapy. However, variable sensitivity of tumor cells exists in this therapy probably due to differences in the expression of proteasome subunits. G alpha(12/13) serves modulators or signal transducers in diverse pathways. This study investigated whether cancer cells display differential sensitivity to bortezomib with reference to G alpha(12/13) expression, and if so, whether G alpha(12/13) affects the expression of proteasome subunits and their activities. Bortezomib treatment exhibited greater sensitivities in Huh7 and SNU886 cells (epithelial type) than SK-Hep1 and SNU449 cells (mesenchymal type) that exhibited higher levels of G alpha(12/13). Overexpression of an active mutant of G alpha(12) (G alpha(12)QL) or G alpha(13) (G alpha(13)QL) diminished the ability of bortezomib to induce cytotoxicity in Huh7 cells. Moreover, transfection with the minigene that disturbs G protein-coupled receptor-G protein coupling (CT12 or CT13) increased it in SK-Hep1 cells. Consistently, MiaPaCa2 cells transfected with CT12 or CT13 exhibited a greater sensitivity to bortezomib. Evidence of G alpha(12/13)'s antagonism on the anticancer effect of bortezomib was verified in the reversal by G alpha(12)QL or G alpha(13)QL of the minigenes' enhancement of cytotoxity. Real-time polymerase chain reaction assay enabled us to identify PSMB5, multicatalytic endopeptidase complex-like-1, and proteasome activator subunit-1 repression by CT12 or CT13. Furthermore, G alpha(12/13) inhibition enhanced the ability of bortezomib to repress PSMB5, as shown by immunoblotting and proteasome activity assay. Moreover, this inhibitory effect on PSMB5 was attenuated by G alpha(12)QL or G alpha(13)QL. In conclusion, the inhibition of G alpha(12/13) activities may enhance the anticancer effect of bortezomib through PSMB5 repression, providing insight into the G alpha(12/13) pathway for the regulation of proteasomal activity. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | OXFORD UNIV PRESS | - |
dc.title | G alpha(12/13) inhibition enhances the anticancer effect of bortezomib through PSMB5 downregulation | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Chang Ho | - |
dc.identifier.doi | 10.1093/carcin/bgq097 | - |
dc.identifier.scopusid | 2-s2.0-77954368003 | - |
dc.identifier.wosid | 000279473100008 | - |
dc.identifier.bibliographicCitation | CARCINOGENESIS, v.31, no.7, pp.1230 - 1237 | - |
dc.relation.isPartOf | CARCINOGENESIS | - |
dc.citation.title | CARCINOGENESIS | - |
dc.citation.volume | 31 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 1230 | - |
dc.citation.endPage | 1237 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.subject.keywordPlus | HETEROTRIMERIC G-PROTEINS | - |
dc.subject.keywordPlus | HEPATOCELLULAR-CARCINOMA | - |
dc.subject.keywordPlus | MESENCHYMAL TRANSITION | - |
dc.subject.keywordPlus | PANCREATIC-CANCER | - |
dc.subject.keywordPlus | LYSOPHOSPHATIDIC ACID | - |
dc.subject.keywordPlus | PROTEASOME INHIBITORS | - |
dc.subject.keywordPlus | SIGNALING PATHWAY | - |
dc.subject.keywordPlus | PROSTATE-CANCER | - |
dc.subject.keywordPlus | 26S PROTEASOME | - |
dc.subject.keywordPlus | SOLID TUMORS | - |
dc.identifier.url | https://academic.oup.com/carcin/article/31/7/1230/2477347 | - |
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