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Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction
Cited 44 time in
Web of Science
Cited 48 time in Scopus
- Authors
- Issue Date
- 2014-01
- Publisher
- Nature Publishing Group
- Citation
- Nature Chemical Biology Vol.10 No.1, pp. 29-34
- Keywords
- 복합학
- Abstract
- Lysyl-tRNA synthetase (KRS), a protein synthesis enzyme in the cytosol, relocates to the plasma membrane after a laminin signal and stabilizes a 67-kDa laminin receptor (67LR) that is implicated in cancer metastasis; however, its potential as an antimetastatic therapeutic target has not been explored. We found that the small compound BC-K-YH16899, which binds KRS, impinged on the interaction of KRS with 67LR and suppressed metastasis in three different mouse models. The compound inhibited the KRS-67LR interaction in two ways. First, it directly blocked the association between KRS and 67LR. Second, it suppressed the dynamic movement of the N-terminal extension of KRS and reduced membrane localization of KRS. However, it did not affect the catalytic activity of KRS. Our results suggest that specific modulation of a cancer-related KRS-67LR interaction may offer a way to control metastasis while avoiding the toxicities associated with inhibition of the normal functions of KRS.
- ISSN
- 1552-4450 (print)
1552-4469 (print)
- Language
- English
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