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Characterization of proteins that interact with the cell-cycle regulatory protein Ran/TC4

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Abstract

THE human Ras-related nuclear protein Ran/TC4 (refs 1–4) is the prototype of a well conserved family of GTPases that can regulate both cell-cycle progression5–8 and messenger RNA transport9. Ran has been proposed to undergo tightly controlled cycles of GTP binding and hydrolysis, to operate as a GTPase switch10,11 whose GTP- and GDP-bound forms interact differentially with regulators and effectors. One known regulator, the protein RCC1 (refs 12, 13), interacts with Ran to catalyse guanine nucleotide exchange, and both RCC1 and Ran are components of an intrinsic checkpoint control that prevents the premature initiation of mitosis. To test and extend the GTPase-switch model, we searched for a Ran-specific GTPase-activating protein (GAP), and for putative effectors (proteins that interact specifically with Ran/TC4–GTP). We report here the identification of a Ran GAP and its use to characterize the GTP-hydrolysing properties of mutant Ran proteins, and the identification and cloning of a binding protein specific for Ran/TC4–GTP.

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Authors and Affiliations

  1. Department of Biochemistry, NYU Medical Center, New York, New York, 10016, USA

    Elias Coutavas, Peter D'Eustachio & Mark G. Rush

  2. Department of Cell Biology, NYU Medical Center, New York, New York, 10016, USA

    Mindong Ren

  3. Department of Microbiology, NYU Medical Center, New York, New York, 10016, USA

    Joel D. Oppenheim

  4. Kaplan Cancer Center, NYU Medical Center, New York, New York, 10016, USA

    Peter D'Eustachio & Mark G. Rush

Authors
  1. Elias Coutavas
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  2. Mindong Ren
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  3. Joel D. Oppenheim
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  4. Peter D'Eustachio
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  5. Mark G. Rush
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Coutavas, E., Ren, M., Oppenheim, J. et al. Characterization of proteins that interact with the cell-cycle regulatory protein Ran/TC4. Nature 366, 585–587 (1993). https://doi.org/10.1038/366585a0

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