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Mitotic Control by Ran and RanBP1 in Mammalian Cells

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The Small GTPase Ran

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Abstract

Growing evidence from model systems indicates mitotic roles for the Ran network independent of nuclear transport. Ran binding protein 1 (RanBPl) is a regulatory component which modulates nucleotide turnover on Ran, and hence its functional state. In mammalian cells, deregulated RanBP1 activity and, more generally, dysfunction of the Ran network, yield mitotic aberrations and genetically imbalanced cells, which are discussed in this chapter. The mammalian RanBP1 gene is subject to growth-dependent and cell cycle phase-dependent control: RanBP1 gene transcription is linked to the basal cell cycle machinery under the control of E2F and pRb (retinoblastoma) factors, which are major regulators of the Gl/S transition. RanBPl protein levels increase from S phase until late telophase, when the protein is no longer detected in daughter nuclei. The cell cycle regulated pattern of RanBPl activity can be disrupted by either overexpressing exogenous constructs or inactivating the endogenous protein. Both types of alterations impair steps of mitotic control, yielding spindles with abnormal poles, impairment of microtubule dynamics during mitosis, blockage or delay of mitotic progression, and failure of chromatin decondensation in daughter nuclei during mitotic exit. Several types of solid tumors show high frequencies of aneuploidy. RanBPl is overexpressed in at least certain transformed cell types. In the future it will be important to assess whether deregulation of RanBPl activity predisposes cells to develop genomic abnormalities during transformation.

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Author information

Authors and Affiliations

  1. Center of Evolutionary Genetics, CNR National Research Council, c/o University “La Sapienza”, Rome, Italy

    Barbara Di Fiore & Patrizia Lavia

  2. Department of Cell Biology, Max-Planck Institute for Biochemistry, Martinsried, Germany

    Giulia Guarguaglini

Authors
  1. Barbara Di Fiore
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  2. Giulia Guarguaglini
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  3. Patrizia Lavia
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Editors and Affiliations

  1. New York University School of Medicine, New York, NY, USA

    Mark Rush  & Peter D’Eustachio  & 

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Di Fiore, B., Guarguaglini, G., Lavia, P. (2001). Mitotic Control by Ran and RanBP1 in Mammalian Cells. In: Rush, M., D’Eustachio, P. (eds) The Small GTPase Ran. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1501-2_8

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  • DOI: https://doi.org/10.1007/978-1-4615-1501-2_8

  • Publisher Name: Springer, Boston, MA

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