Ran GTPase in Nuclear Envelope Formation and Cancer Metastasis

KB Matchett, S McFarlane, SE Hamilton, YS Eltuhamy, MA Davidson, JT Murray, A. M. Faheem, M El-Tanani

    Research output: Chapter in Book/Report/Conference proceedingChapter

    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
    Title of host publicationCancer Biology and the Nuclear Envelope - Recent Advances May Elucidate Past Paradoxes
    Pages323 -351
    Volume773
    DOIs
    Publication statusPublished - 2014

    Fingerprint

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

    Keywords

    • Ran GTPace. Nucleocytoplasmic transport. Mitoptic spindle. Nuclear envelope
    • RCC1
    • RanBP1
    • CRM1
    • TPX2. Importin-beta. Cell cycle checkpoint control. Ostepontin. Metastasis.

    Cite this

    Matchett, KB., McFarlane, S., Hamilton, SE., Eltuhamy, YS., Davidson, MA., Murray, JT., ... El-Tanani, M. (2014). Ran GTPase in Nuclear Envelope Formation and Cancer Metastasis. In Cancer Biology and the Nuclear Envelope - Recent Advances May Elucidate Past Paradoxes (Vol. 773, pp. 323 -351) https://doi.org/10.1007/978-1-4899-8032-8
    Matchett, KB ; McFarlane, S ; Hamilton, SE ; Eltuhamy, YS ; Davidson, MA ; Murray, JT ; Faheem, A. M. ; El-Tanani, M. / Ran GTPase in Nuclear Envelope Formation and Cancer Metastasis. Cancer Biology and the Nuclear Envelope - Recent Advances May Elucidate Past Paradoxes. Vol. 773 2014. 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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    author = "KB Matchett and S McFarlane and SE Hamilton and YS Eltuhamy and MA Davidson and JT Murray and Faheem, {A. M.} and M El-Tanani",
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    Matchett, KB, McFarlane, S, Hamilton, SE, Eltuhamy, YS, Davidson, MA, Murray, JT, Faheem, AM & El-Tanani, M 2014, Ran GTPase in Nuclear Envelope Formation and Cancer Metastasis. in Cancer Biology and the Nuclear Envelope - Recent Advances May Elucidate Past Paradoxes. vol. 773, pp. 323 -351. https://doi.org/10.1007/978-1-4899-8032-8

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

    Cancer Biology and the Nuclear Envelope - Recent Advances May Elucidate Past Paradoxes. Vol. 773 2014. p. 323 -351.

    Research output: Chapter in Book/Report/Conference proceedingChapter

    TY - CHAP

    T1 - Ran GTPase in Nuclear Envelope Formation and Cancer Metastasis

    AU - Matchett, KB

    AU - McFarlane, S

    AU - Hamilton, SE

    AU - Eltuhamy, YS

    AU - Davidson, MA

    AU - Murray, JT

    AU - Faheem, A. M.

    AU - El-Tanani, M

    PY - 2014

    Y1 - 2014

    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.

    AB - 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.

    KW - Ran GTPace. Nucleocytoplasmic transport. Mitoptic spindle. Nuclear envelope

    KW - RCC1

    KW - RanBP1

    KW - CRM1

    KW - TPX2. Importin-beta. Cell cycle checkpoint control. Ostepontin. Metastasis.

    U2 - 10.1007/978-1-4899-8032-8

    DO - 10.1007/978-1-4899-8032-8

    M3 - Chapter

    SN - 978-1-4899-8032-8

    VL - 773

    SP - 323

    EP - 351

    BT - Cancer Biology and the Nuclear Envelope - Recent Advances May Elucidate Past Paradoxes

    ER -

    Matchett KB, McFarlane S, Hamilton SE, Eltuhamy YS, Davidson MA, Murray JT et al. Ran GTPase in Nuclear Envelope Formation and Cancer Metastasis. In Cancer Biology and the Nuclear Envelope - Recent Advances May Elucidate Past Paradoxes. Vol. 773. 2014. p. 323 -351 https://doi.org/10.1007/978-1-4899-8032-8