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, H.E. | - |
dc.contributor.author | Lee, Y. | - |
dc.contributor.author | Kim, E. | - |
dc.contributor.author | Cho, C.Y. | - |
dc.contributor.author | Jung, O. | - |
dc.contributor.author | Lee, D. | - |
dc.contributor.author | Lee, E.G. | - |
dc.contributor.author | Nam, S.H. | - |
dc.contributor.author | Kang, M. | - |
dc.contributor.author | Macalino, S.J.Y. | - |
dc.contributor.author | Kim, J.E. | - |
dc.contributor.author | Jung, J.W. | - |
dc.contributor.author | Kwon, S.W. | - |
dc.contributor.author | Choi, S. | - |
dc.contributor.author | Lee, J.W. | - |
dc.date.accessioned | 2023-03-08T12:02:08Z | - |
dc.date.available | 2023-03-08T12:02:08Z | - |
dc.date.issued | 2021 | - |
dc.identifier.issn | 1838-7640 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/62875 | - |
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. © 2021 Ivyspring International Publisher. All rights reserved. | - |
dc.format.extent | 20 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
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.identifier.bibliographicCitation | Theranostics, v.11, no.16, pp 8092 - 8111 | - |
dc.description.isOpenAccess | N | - |
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.title | Theranostics | - |
dc.citation.volume | 11 | - |
dc.type.docType | Article | - |
dc.publisher.location | 호주 | - |
dc.subject.keywordAuthor | c-Src | - |
dc.subject.keywordAuthor | Metastasis | - |
dc.subject.keywordAuthor | Protein-protein interaction | - |
dc.subject.keywordAuthor | PTPIB | - |
dc.subject.keywordAuthor | TM4SF5 | - |
dc.subject.keywordPlus | c Src proto oncogene | - |
dc.subject.keywordPlus | cell penetrating peptide | - |
dc.subject.keywordPlus | focal adhesion kinase | - |
dc.subject.keywordPlus | membrane protein | - |
dc.subject.keywordPlus | protein tyrosine kinase | - |
dc.subject.keywordPlus | protein tyrosine phosphatase 1B | - |
dc.subject.keywordPlus | tetraspanin | - |
dc.subject.keywordPlus | transmembrane 4 L six family member 5 | - |
dc.subject.keywordPlus | unclassified drug | - |
dc.subject.keywordPlus | amino terminal sequence | - |
dc.subject.keywordPlus | animal experiment | - |
dc.subject.keywordPlus | animal model | - |
dc.subject.keywordPlus | animal tissue | - |
dc.subject.keywordPlus | Article | - |
dc.subject.keywordPlus | carboxy terminal sequence | - |
dc.subject.keywordPlus | controlled study | - |
dc.subject.keywordPlus | enzyme activation | - |
dc.subject.keywordPlus | enzyme phosphorylation | - |
dc.subject.keywordPlus | enzyme regulation | - |
dc.subject.keywordPlus | female | - |
dc.subject.keywordPlus | gene mutation | - |
dc.subject.keywordPlus | human | - |
dc.subject.keywordPlus | human cell | - |
dc.subject.keywordPlus | in vivo study | - |
dc.subject.keywordPlus | liver cell carcinoma | - |
dc.subject.keywordPlus | lung metastasis | - |
dc.subject.keywordPlus | male | - |
dc.subject.keywordPlus | molecular dynamics | - |
dc.subject.keywordPlus | mouse | - |
dc.subject.keywordPlus | nonhuman | - |
dc.subject.keywordPlus | prediction | - |
dc.subject.keywordPlus | protein binding | - |
dc.subject.keywordPlus | protein dephosphorylation | - |
dc.subject.keywordPlus | protein domain | - |
dc.subject.keywordPlus | protein protein interaction | - |
dc.subject.keywordPlus | protein structure | - |
dc.subject.keywordPlus | sequence homology | - |
dc.subject.keywordPlus | tumor growth | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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