Targeting the interaction of AIMP2-DX2 with HSP70 suppresses cancer development
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lim, Semi | - |
dc.contributor.author | Cho, Hye Young | - |
dc.contributor.author | Kim, Dae Gyu | - |
dc.contributor.author | Roh, Younah | - |
dc.contributor.author | Son, Se-Young | - |
dc.contributor.author | Ul Mushtaq, Ameeq | - |
dc.contributor.author | Kim, Minkyoung | - |
dc.contributor.author | Bhattarai, Deepak | - |
dc.contributor.author | Sivaraman, Aneesh | - |
dc.contributor.author | Lee, Youngjin | - |
dc.contributor.author | Lee, Jihye | - |
dc.contributor.author | Yang, Won Suk | - |
dc.contributor.author | Kim, Hoi Kyoung | - |
dc.contributor.author | Kim, Myung Hee | - |
dc.contributor.author | Lee, Kyeong | - |
dc.contributor.author | Jeon, Young Ho | - |
dc.contributor.author | Kim, Sunghoon | - |
dc.date.accessioned | 2021-08-31T14:54:15Z | - |
dc.date.available | 2021-08-31T14:54:15Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2020-01 | - |
dc.identifier.issn | 1552-4450 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/58430 | - |
dc.description.abstract | A tumorigenic factor, AIMP2 lacking exon 2 (AIMP2-DX2), is often upregulated in many cancers. However, how its cellular level is determined is not understood. Here, we report heat-shock protein HSP70 as a critical determinant for the level of AIMP2-DX2. Interaction of the two factors was identified by interactome analysis and structurally determined by X-ray crystallography and NMR analyses. HSP70 recognizes the amino (N)-terminal flexible region, as well as the glutathione S-transferase domain of AIMP2-DX2, via its substrate-binding domain, thus blocking the Siahl-dependent ubiquitination of AIMP2-DX2. AIMP2-DX2-induced cell transformation and cancer progression in vivo was further augmented by HSP70. A positive correlation between HSP70 and AIMP2-DX2 levels was shown in various lung cancer cell lines and patient tissues. Chemical intervention in the AIMP2-DX2-HSP70 interaction suppressed cancer cell growth in vitro and in vivo. Thus, this work demonstrates the importance of the interaction between AIMP2-DX2 and HSP70 on tumor progression and its therapeutic potential against cancer. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | HEAT-SHOCK PROTEINS | - |
dc.subject | TRANSFER-RNA SYNTHETASES | - |
dc.subject | SPLICING VARIANT | - |
dc.subject | MOLECULAR CHAPERONES | - |
dc.subject | PROMOTE CANCER | - |
dc.subject | BINDING | - |
dc.subject | CLIENT | - |
dc.subject | TUMORIGENESIS | - |
dc.subject | AIMP2/P38 | - |
dc.subject | APOPTOSIS | - |
dc.title | Targeting the interaction of AIMP2-DX2 with HSP70 suppresses cancer development | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Jeon, Young Ho | - |
dc.identifier.doi | 10.1038/s41589-019-0415-2 | - |
dc.identifier.scopusid | 2-s2.0-85076179555 | - |
dc.identifier.wosid | 000503057200011 | - |
dc.identifier.bibliographicCitation | NATURE CHEMICAL BIOLOGY, v.16, no.1, pp.31 - + | - |
dc.relation.isPartOf | NATURE CHEMICAL BIOLOGY | - |
dc.citation.title | NATURE CHEMICAL BIOLOGY | - |
dc.citation.volume | 16 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 31 | - |
dc.citation.endPage | + | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.subject.keywordPlus | HEAT-SHOCK PROTEINS | - |
dc.subject.keywordPlus | TRANSFER-RNA SYNTHETASES | - |
dc.subject.keywordPlus | SPLICING VARIANT | - |
dc.subject.keywordPlus | MOLECULAR CHAPERONES | - |
dc.subject.keywordPlus | PROMOTE CANCER | - |
dc.subject.keywordPlus | BINDING | - |
dc.subject.keywordPlus | CLIENT | - |
dc.subject.keywordPlus | TUMORIGENESIS | - |
dc.subject.keywordPlus | AIMP2/P38 | - |
dc.subject.keywordPlus | APOPTOSIS | - |
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