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N-terminus-independent activation of c-Src via binding to a tetraspan(in) TM4SF5 in hepatocellular carcinoma is abolished by the TM4SF5 C-terminal peptide application
DC Field | Value | Language |
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dc.contributor.author | Song, Haeng Eun | - |
dc.contributor.author | Lee, Yoonji | - |
dc.contributor.author | Kim, Eunmi | - |
dc.contributor.author | Cho, Chang Yun | - |
dc.contributor.author | Jung, Oisun | - |
dc.contributor.author | Lee, Doohyung | - |
dc.contributor.author | Lee, Eun Goo | - |
dc.contributor.author | Nam, Seo Hee | - |
dc.contributor.author | Kang, Minkyung | - |
dc.contributor.author | Macalino, Stephani Joy Y. | - |
dc.contributor.author | Kim, Ji Eon | - |
dc.contributor.author | Jung, Jae Woo | - |
dc.contributor.author | Kwon, Sung Won | - |
dc.contributor.author | Choi, Sun | - |
dc.contributor.author | Lee, Jung Weon | - |
dc.date.accessioned | 2023-04-19T02:08:20Z | - |
dc.date.available | 2023-04-19T02:08:20Z | - |
dc.date.created | 2021-09-16 | - |
dc.date.issued | 2021-01 | - |
dc.identifier.citation | Theranostics, Vol.11 No.16, pp.8092-8111 | - |
dc.identifier.issn | 1838-7640 | - |
dc.identifier.uri | https://hdl.handle.net/10371/190458 | - |
dc.description.abstract | Active c-Src non-receptor tyrosine kinase localizes to the plasma membrane via N-terminal lipid modification. Membranous c-Src causes cancer initiation and progression. Even though transmembrane 4 L six family member 5 (TM4SF5), a tetraspan(in), can be involved in this mechanism, the molecular and structural influence of TM4SF5 on c-Src remains unknown. Methods: Here, we investigated molecular and structural details by which TM4SF5 regulated c-Src devoid of its N-terminus and how cell-penetrating peptides were able to interrupt c-Src activation via interference of c-Src-TM4SF5 interaction in hepatocellular carcinoma models. Results: The TM4SF5 C-terminus efficiently bound the c-Src SH1 kinase domain, efficiently to the inactively-closed form. The complex involved protein tyrosine phosphatase 1B able to dephosphorylate Tyr530. The c-Src SH1 domain alone, even in a closed form, bound TM4SF5 to cause c-Src Tyr419 and FAK Y861 phosphorylation. Homology modeling and molecular dynamics simulation studies predicted the directly interfacing residues, which were further validated by mutational studies. Cell penetration of TM4SF5 C-terminal peptides blocked the interaction of TM4SF5 with c-Src and prevented c-Src-dependent tumor initiation and progression in vivo. Conclusions: Collectively, these data demonstrate that binding of the TM4SF5 C-terminus to the kinase domain of inactive c-Src leads to its activation. Because this binding can be abolished by cell-penetrating peptides containing the TM4SF5 C-terminus, targeting this direct interaction may be an effective strategy for developing therapeutics that block the development and progression of hepatocellular carcinoma. | - |
dc.language | 영어 | - |
dc.publisher | Ivyspring International Publisher | - |
dc.title | N-terminus-independent activation of c-Src via binding to a tetraspan(in) TM4SF5 in hepatocellular carcinoma is abolished by the TM4SF5 C-terminal peptide application | - |
dc.type | Article | - |
dc.identifier.doi | 10.7150/thno.58739 | - |
dc.citation.journaltitle | Theranostics | - |
dc.identifier.wosid | 000692582300014 | - |
dc.identifier.scopusid | 2-s2.0-85112214392 | - |
dc.citation.endpage | 8111 | - |
dc.citation.number | 16 | - |
dc.citation.startpage | 8092 | - |
dc.citation.volume | 11 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Kwon, Sung Won | - |
dc.contributor.affiliatedAuthor | Lee, Jung Weon | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | EPITHELIAL-MESENCHYMAL TRANSITION | - |
dc.subject.keywordPlus | MULTIPLE SEQUENCE ALIGNMENT | - |
dc.subject.keywordPlus | TYROSINE KINASE STRUCTURE | - |
dc.subject.keywordPlus | PROTEIN-KINASE | - |
dc.subject.keywordPlus | CELL-TRANSFORMATION | - |
dc.subject.keywordPlus | ADHESION KINASE | - |
dc.subject.keywordPlus | FAMILY KINASES | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | HEPATOCYTES | - |
dc.subject.keywordPlus | GROMACS | - |
dc.subject.keywordAuthor | c-Src | - |
dc.subject.keywordAuthor | metastasis | - |
dc.subject.keywordAuthor | protein-protein interaction | - |
dc.subject.keywordAuthor | PTPIB | - |
dc.subject.keywordAuthor | TM4SF5 | - |
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