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Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction.
Kim, Dae Gyu; Lee, Jin Young; Kwon, Nam Hoon; Fang, Pengfei; Zhang, Qian; Wang, Jing; Young, Nicolas L; Guo, Min; Cho, Hye Young; Mushtaq, Ameeq Ul; Jeon, Young Ho; Choi, Jin Woo; Han, Jung Min; Kang, Ho Woong; Joo, Jae Eun; Hur, Youn; Kang, Wonyoung; Yang, Heekyoung; Nam, Do-Hyun; Lee, Mi-Sook; Lee, Jung Weon; Kim, Eun-Sook; Moon, Aree; Kim, Kibom; Kim, Doyeun; Kang, Eun Joo; Moon, Youngji; Rhee, Kyung Hee; Han, Byung Woo; Yang, Jee Sun; Han, Gyoonhee; Yang, Won Suk; Lee, Cheolju; Wang, Ming-Wei; Kim, Sunghoon.
Afiliação
  • Kim DG; 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea. [3].
  • Lee JY; 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea. [3].
  • Kwon NH; 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
  • Fang P; Department of Cancer Biology, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, USA.
  • Zhang Q; Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, USA.
  • Wang J; Department of Cancer Biology, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, USA.
  • Young NL; Ion Cyclotron Resonance Program, National High Magnetic Field Laboratory, Florida State University, Tallahassee, Florida, USA.
  • Guo M; Department of Cancer Biology, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, USA.
  • Cho HY; College of Pharmacy, Korea University, Sejong, Korea.
  • Mushtaq AU; College of Pharmacy, Korea University, Sejong, Korea.
  • Jeon YH; College of Pharmacy, Korea University, Sejong, Korea.
  • Choi JW; 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Han JM; 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
  • Kang HW; Yuhan Research Institute, Yongin, Korea.
  • Joo JE; Yuhan Research Institute, Yongin, Korea.
  • Hur Y; Yuhan Research Institute, Yongin, Korea.
  • Kang W; Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • Yang H; Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • Nam DH; Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • Lee MS; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
  • Lee JW; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
  • Kim ES; College of Pharmacy, Duksung Women's University, Seoul, Korea.
  • Moon A; College of Pharmacy, Duksung Women's University, Seoul, Korea.
  • Kim K; 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
  • Kim D; 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
  • Kang EJ; Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea.
  • Moon Y; Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea.
  • Rhee KH; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
  • Han BW; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
  • Yang JS; Translational Research Center for Protein Function Control, Department of Biotechnology and WCU Department of Biomedical Sciences, Yonsei University, Seoul, Korea.
  • Han G; Translational Research Center for Protein Function Control, Department of Biotechnology and WCU Department of Biomedical Sciences, Yonsei University, Seoul, Korea.
  • Yang WS; 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
  • Lee C; BRI, Korea Institute of Science and Technology, Seoul, Korea.
  • Wang MW; The National Center for Drug Screening, Zhangjiang High-Tech Park, Shanghai, China.
  • Kim S; 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea. [3] World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul Nat
Nat Chem Biol ; 10(1): 29-34, 2014 Jan.
Article em En | MEDLINE | ID: mdl-24212136
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de Laminina / Lisina-tRNA Ligase / Metástase Neoplásica Idioma: En Revista: Nat Chem Biol Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de Laminina / Lisina-tRNA Ligase / Metástase Neoplásica Idioma: En Revista: Nat Chem Biol Ano de publicação: 2014 Tipo de documento: Article