Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 최선 | * |
dc.contributor.author | 이윤지 | * |
dc.date.accessioned | 2021-11-10T16:31:03Z | - |
dc.date.available | 2021-11-10T16:31:03Z | - |
dc.date.issued | 2021 | * |
dc.identifier.issn | 1838-7640 | * |
dc.identifier.other | OAK-30141 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/259306 | - |
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 | English | * |
dc.publisher | IVYSPRING INT PUBL | * |
dc.subject | c-Src | * |
dc.subject | metastasis | * |
dc.subject | protein-protein interaction | * |
dc.subject | PTPIB | * |
dc.subject | TM4SF5 | * |
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.relation.issue | 16 | * |
dc.relation.volume | 11 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 8092 | * |
dc.relation.lastpage | 8111 | * |
dc.relation.journaltitle | THERANOSTICS | * |
dc.identifier.doi | 10.7150/thno.58739 | * |
dc.identifier.wosid | WOS:000692582300014 | * |
dc.author.google | Song, Haeng Eun | * |
dc.author.google | Lee, Yoonji | * |
dc.author.google | Kim, Eunmi | * |
dc.author.google | Cho, Chang Yun | * |
dc.author.google | Jung, Oisun | * |
dc.author.google | Lee, Doohyung | * |
dc.author.google | Lee, Eun Goo | * |
dc.author.google | Nam, Seo Hee | * |
dc.author.google | Kang, Minkyung | * |
dc.author.google | Macalino, Stephani Joy Y. | * |
dc.author.google | Kim, Ji Eon | * |
dc.author.google | Jung, Jae Woo | * |
dc.author.google | Kwon, Sung Won | * |
dc.author.google | Choi, Sun | * |
dc.author.google | Lee, Jung Weon | * |
dc.contributor.scopusid | 최선(8659831000) | * |
dc.contributor.scopusid | 이윤지(16836651600) | * |
dc.date.modifydate | 20240305081003 | * |