| Literature DB >> 24212136 |
Dae Gyu Kim1, Jin Young Lee1, Nam Hoon Kwon2, Pengfei Fang3, Qian Zhang4, Jing Wang3, Nicolas L Young5, Min Guo3, Hye Young Cho6, Ameeq Ul Mushtaq6, Young Ho Jeon6, Jin Woo Choi7, Jung Min Han2, Ho Woong Kang8, Jae Eun Joo8, Youn Hur8, Wonyoung Kang9, Heekyoung Yang9, Do-Hyun Nam9, Mi-Sook Lee10, Jung Weon Lee10, Eun-Sook Kim11, Aree Moon11, Kibom Kim2, Doyeun Kim2, Eun Joo Kang12, Youngji Moon12, Kyung Hee Rhee10, Byung Woo Han10, Jee Sun Yang13, Gyoonhee Han13, Won Suk Yang2, Cheolju Lee14, Ming-Wei Wang15, Sunghoon Kim16.
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.Entities:
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Year: 2013 PMID： 24212136 PMCID： PMC4021855 DOI： 10.1038/nchembio.1381
Source DB: PubMed Journal: Nat Chem Biol ISSN： 1552-4450 Impact factor: 15.040