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- Joseph Heitman
- Department of Biochemistry, Biocenter of the University of Basel, CH4056 Basel, Switzerland.
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- N. Rao Movva
- Preclinical Research, Sandoz Pharma Limited, CH-4002 Basel, Switzerland
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- Michael N. Hall
- Department of Biochemistry, Biocenter of the University of Basel, CH4056 Basel, Switzerland.
書誌事項
- 公開日
- 1991-08-23
- DOI
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- 10.1126/science.1715094
- 公開者
- American Association for the Advancement of Science (AAAS)
この論文をさがす
説明
<jats:p> FK506 and rapamycin are related immunosuppressive compounds that block helper T cell activation by interfering with signal transduction. In vitro, both drugs bind and inhibit the FK506-binding protein (FKBP) proline rotamase. <jats:italic>Saccharomyces cerevisiae</jats:italic> cells treated with rapamycin irreversibly arrested in the G1 phase of the cell cycle. An FKBP-rapamycin complex is concluded to be the toxic agent because (i) strains that lack FKBP proline rotamase, encoded by <jats:italic>FPR1</jats:italic> , were viable and fully resistant to rapamycin and (ii) FK506 antagonized rapamycin toxicity in vivo. Mutations that conferred rapamycin resistance altered conserved residues in FKBP that are critical for drug binding. Two genes other than <jats:italic>FPR1</jats:italic> , named <jats:italic>TOR1</jats:italic> and <jats:italic>TOR2</jats:italic> , that participate in rapamycin toxicity were identified. Nonallelic noncomplementation between <jats:italic>FPR1</jats:italic> , <jats:italic>TOR1</jats:italic> , and <jats:italic>TOR2</jats:italic> alleles suggests that the products of these genes may interact as subunits of a protein complex. Such a complex may mediate nuclear entry of signals required for progression through the cell cycle. </jats:p>
収録刊行物
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- Science
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Science 253 (5022), 905-909, 1991-08-23
American Association for the Advancement of Science (AAAS)
