Ran GTPase in Nuclear Envelope Formation and Cancer Metastasis

KB Matchett, S McFarlane, SE Hamilton, YS Eltuhamy, MA Davidson, IT Murray, Ahmed Faheem, M El-Tanani

    Research output: Contribution to journalArticle

    19 Citations (Scopus)

    Abstract

    Ran is a small ras-related GTPase that controls the nucleocytoplasmic exchange of macromolecules across the nuclear envelope. It binds to chromatin early during nuclear formation and has important roles during the eukaryotic cell cycle, where it regulates mitotic spindle assembly, nuclear envelope formation and cell cycle checkpoint control. Like other GTPases, Ran relies on the cycling between GTP-bound and GDP-bound conformations to interact with effector proteins and regulate these processes. In nucleocytoplasmic transport, Ran shuttles across the nuclear envelope through nuclear pores. It is concentrated in the nucleus by an active import mechanism where it generates a high concentration of RanGTP by nucleotide exchange. It controls the assembly and disassembly of a range of complexes that are formed between Ran-binding proteins and cellular cargo to maintain rapid nuclear transport. Ran also has been identified as an essential protein in nuclear envelope formation in eukaryotes. This mechanism is dependent on importin-β, which regulates the assembly of further complexes important in this process, such as Nup107-Nup160. A strong body of evidence is emerging implicating Ran as a key protein in the metastatic progression of cancer. Ran is overexpressed in a range of tumors, such as breast and renal, and these perturbed levels are associated with local invasion, metastasis and reduced patient survival. Furthermore, tumors with oncogenic KRAS or PIK3CA mutations are addicted to Ran expression, which yields exciting future therapeutic opportunities.
    LanguageEnglish
    Pages323-351
    JournalAdvances in Experiment Medicine and Biology
    Volume773
    DOIs
    Publication statusPublished - 24 Jan 2014

    Fingerprint

    GTP Phosphohydrolases
    Nuclear Envelope
    Neoplasm Metastasis
    Monomeric GTP-Binding Proteins
    Cell Nucleus Active Transport
    Tumors
    Cell Cycle Checkpoints
    beta Karyopherins
    Cells
    Neoplasms
    Proteins
    ran GTP-Binding Protein
    Guanosine Triphosphate
    Macromolecules
    Nuclear Pore
    Spindle Apparatus
    Chromatin
    Conformations
    Carrier Proteins
    Eukaryotic Cells

    Keywords

    • Ran GTPase Nucleocytoplasmic transport Mitotic spindle Nuclear envelope RCC1 RanBP1 CRM1 TPX2 Importin-β Cell cycle checkpoint control Osteopontin Metastasis

    Cite this

    Matchett, KB., McFarlane, S., Hamilton, SE., Eltuhamy, YS., Davidson, MA., Murray, IT., ... El-Tanani, M. (2014). Ran GTPase in Nuclear Envelope Formation and Cancer Metastasis. Advances in Experiment Medicine and Biology, 773, 323-351. https://doi.org/10.1007/978-1-4899-8032-8_15
    Matchett, KB ; McFarlane, S ; Hamilton, SE ; Eltuhamy, YS ; Davidson, MA ; Murray, IT ; Faheem, Ahmed ; El-Tanani, M. / Ran GTPase in Nuclear Envelope Formation and Cancer Metastasis. In: Advances in Experiment Medicine and Biology. 2014 ; Vol. 773. pp. 323-351.
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    abstract = "Ran is a small ras-related GTPase that controls the nucleocytoplasmic exchange of macromolecules across the nuclear envelope. It binds to chromatin early during nuclear formation and has important roles during the eukaryotic cell cycle, where it regulates mitotic spindle assembly, nuclear envelope formation and cell cycle checkpoint control. Like other GTPases, Ran relies on the cycling between GTP-bound and GDP-bound conformations to interact with effector proteins and regulate these processes. In nucleocytoplasmic transport, Ran shuttles across the nuclear envelope through nuclear pores. It is concentrated in the nucleus by an active import mechanism where it generates a high concentration of RanGTP by nucleotide exchange. It controls the assembly and disassembly of a range of complexes that are formed between Ran-binding proteins and cellular cargo to maintain rapid nuclear transport. Ran also has been identified as an essential protein in nuclear envelope formation in eukaryotes. This mechanism is dependent on importin-β, which regulates the assembly of further complexes important in this process, such as Nup107-Nup160. A strong body of evidence is emerging implicating Ran as a key protein in the metastatic progression of cancer. Ran is overexpressed in a range of tumors, such as breast and renal, and these perturbed levels are associated with local invasion, metastasis and reduced patient survival. Furthermore, tumors with oncogenic KRAS or PIK3CA mutations are addicted to Ran expression, which yields exciting future therapeutic opportunities.",
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    Matchett, KB, McFarlane, S, Hamilton, SE, Eltuhamy, YS, Davidson, MA, Murray, IT, Faheem, A & El-Tanani, M 2014, 'Ran GTPase in Nuclear Envelope Formation and Cancer Metastasis', Advances in Experiment Medicine and Biology, vol. 773, pp. 323-351. https://doi.org/10.1007/978-1-4899-8032-8_15

    Ran GTPase in Nuclear Envelope Formation and Cancer Metastasis. / Matchett, KB; McFarlane, S; Hamilton, SE; Eltuhamy, YS; Davidson, MA; Murray, IT; Faheem, Ahmed; El-Tanani, M.

    In: Advances in Experiment Medicine and Biology, Vol. 773, 24.01.2014, p. 323-351.

    Research output: Contribution to journalArticle

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    AU - Matchett, KB

    AU - McFarlane, S

    AU - Hamilton, SE

    AU - Eltuhamy, YS

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    AU - Faheem, Ahmed

    AU - El-Tanani, M

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    N2 - Ran is a small ras-related GTPase that controls the nucleocytoplasmic exchange of macromolecules across the nuclear envelope. It binds to chromatin early during nuclear formation and has important roles during the eukaryotic cell cycle, where it regulates mitotic spindle assembly, nuclear envelope formation and cell cycle checkpoint control. Like other GTPases, Ran relies on the cycling between GTP-bound and GDP-bound conformations to interact with effector proteins and regulate these processes. In nucleocytoplasmic transport, Ran shuttles across the nuclear envelope through nuclear pores. It is concentrated in the nucleus by an active import mechanism where it generates a high concentration of RanGTP by nucleotide exchange. It controls the assembly and disassembly of a range of complexes that are formed between Ran-binding proteins and cellular cargo to maintain rapid nuclear transport. Ran also has been identified as an essential protein in nuclear envelope formation in eukaryotes. This mechanism is dependent on importin-β, which regulates the assembly of further complexes important in this process, such as Nup107-Nup160. A strong body of evidence is emerging implicating Ran as a key protein in the metastatic progression of cancer. Ran is overexpressed in a range of tumors, such as breast and renal, and these perturbed levels are associated with local invasion, metastasis and reduced patient survival. Furthermore, tumors with oncogenic KRAS or PIK3CA mutations are addicted to Ran expression, which yields exciting future therapeutic opportunities.

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    Matchett KB, McFarlane S, Hamilton SE, Eltuhamy YS, Davidson MA, Murray IT et al. Ran GTPase in Nuclear Envelope Formation and Cancer Metastasis. Advances in Experiment Medicine and Biology. 2014 Jan 24;773:323-351. https://doi.org/10.1007/978-1-4899-8032-8_15