Brasilicardin A, a Natural Immunosuppressant, Targets Amino Acid Transport System L

Takeo Usui, Yoko Nagumo, Ai Watanabe, Takaaki Kubota, Kazusei Komatsu, Jun'ichi Kobayashi, Hiroyuki Osada

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Lymphocytes in T cell activation require extracellular nutrients to provide energy for cellular proliferation and effector functions. Therefore, inhibitors of nutrient transporters are expected to be a new class of immunosuppressant. Here, we report that the molecular target of brasilicardin A (BraA), an immunosuppressive compound, is the amino acid transporter system L. BraA inhibited the cell-cycle progression of murine T cell lymphocyte CTLL-2 cells in G1 phase, and potently inhibited the uptake of amino acids that are substrates for amino acid transport system L. Moreover, BraA stimulated the GCN2 activation and, subsequently, the phosphorylation of eIF2α. These results suggest that the immunosuppressive activity of BraA is induced by amino acid deprivation via the inhibition of system L and that the amino acid transporter is a target for immunosuppressant.

Original languageEnglish
Pages (from-to)1153-1160
Number of pages8
JournalChemistry and Biology
Volume13
Issue number11
DOIs
Publication statusPublished - Nov 2006
Externally publishedYes

Keywords

  • CHEMBIO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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