Targeting the interaction of AIMP2-DX2 with HSP70 suppresses cancer development
- Authors
- Lim, Semi; Cho, Hye Young; Kim, Dae Gyu; Roh, Younah; Son, Se-Young; Ul Mushtaq, Ameeq; Kim, Minkyoung; Bhattarai, Deepak; Sivaraman, Aneesh; Lee, Youngjin; Lee, Jihye; Yang, Won Suk; Kim, Hoi Kyoung; Kim, Myung Hee; Lee, Kyeong; Jeon, Young Ho; Kim, Sunghoon
- Issue Date
- 1월-2020
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE CHEMICAL BIOLOGY, v.16, no.1, pp.31 - +
- Indexed
- SCIE
SCOPUS
- Journal Title
- NATURE CHEMICAL BIOLOGY
- Volume
- 16
- Number
- 1
- Start Page
- 31
- End Page
- +
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/58430
- DOI
- 10.1038/s41589-019-0415-2
- ISSN
- 1552-4450
- 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.
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Collections - College of Pharmacy > Department of Pharmaceutical Science > 1. Journal Articles
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