Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Ran

  • Carlo Petosa
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_641

Synonyms

 Gsp1;  Spi1;  TC4

Historical Background

Ran is an abundant member of the Ras superfamily of small GTPases that is highly conserved across eukaryotes. Originally cloned from a human teratocarcinoma cell line as one of four novel genes with sequence homology to the GTP-binding domain of Ras (Drivas et al. 1990), the gene was initially named TC4 (teratocarcinoma clone 4) and found to encode a protein of 216 amino acid residues. TC4 was markedly different from other members of the Ras superfamily in two respects: it lacked the sites required for post-translational lipid modification and it was primarily localized to the nucleus. Accordingly, it was renamed Ran for Ras-related nuclear protein. Ran was subsequently purified as an essential cofactor for nuclear protein import (Moore and Blobel 1993) and over the following years was extensively characterized for its role in regulating nucleocytoplasmic transport. Ran was later discovered to be critical for mitotic spindle assembly...

This is a preview of subscription content, log in to check access.

References

  1. Arnaoutov A, Dasso M. Ran-GTP regulates kinetochore attachment in somatic cells. Cell Cycle. 2005;4:1161–5.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Budhu AS, Wang XW. Loading and unloading: orchestrating centrosome duplication and spindle assembly by Ran/Crm1. Cell Cycle. 2005;4:1510–4.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Carazo-Salas RE, Guarguaglini G, Gruss OJ, Segref A, Karsenti E, Mattaj IW. Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation. Nature. 1999;400:178–81.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Clarke PR, Zhang C. Spatial and temporal coordination of mitosis by Ran GTPase. Nat Rev Mol Cell Biol. 2008;9:464–77.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Cook AG, Conti E. Nuclear export complexes in the frame. Curr Opin Struct Biol. 2010;20:247–52.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Dishinger JF, Kee HL, Jenkins PM, Fan S, Hurd TW, Hammond JW, Truong YN, Margolis B, Martens JR, Verhey KJ. Ciliary entry of the kinesin-2 motor KIF17 is regulated by importin-beta2 and RanGTP. Nat Cell Biol. 2010;12:703–10.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Drivas GT, Shih A, Coutavas E, Rush MG, D’Eustachio P. Characterization of four novel ras-like genes expressed in a human teratocarcinoma cell line. Mol Cell Biol. 1990;10:1793–8.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Fried H, Kutay U. Nucleocytoplasmic transport: taking an inventory. Cell Mol Life Sci. 2003;60:1659–88.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Gruss OJ, Vernos I. The mechanism of spindle assembly: functions of Ran and its target TPX2. J Cell Biol. 2004;166:949–55.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Hetzer M, Bilbao-Cortes D, Walther TC, Gruss OJ, Mattaj IW. GTP hydrolysis by Ran is required for nuclear envelope assembly. Mol Cell. 2000;5:1013–24.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Lavia P, Mileo AM, Giordano A, Paggi MG. Emerging roles of DNA tumor viruses in cell proliferation: new insights into genomic instability. Oncogene. 2003;22:6508–16.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Moore MS, Blobel G. The GTP-binding protein Ran/TC4 is required for protein import into the nucleus. Nature. 1993;365:661–3.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Ohba T, Nakamura M, Nishitani H, Nishimoto T. Self-organization of microtubule asters induced in Xenopus egg extracts by GTP-bound Ran. Science. 1999;284:1356–8.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Roscioli E, Bolognesi A, Guarguaglini G, Lavia P. Ran control of mitosis in human cells: gradients and local signals. Biochem Soc Trans. 2010;38:1709–14.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Stewart M. Molecular mechanism of the nuclear protein import cycle. Nat Rev Mol Cell Biol. 2007;8:195–208.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Walther TC, Askjaer P, Gentzel M, Habermann A, Griffiths G, Wilm M, Mattaj IW, Hetzer M. RanGTP mediates nuclear pore complex assembly. Nature. 2003;424:689–94.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Wittinghofer A, Vetter IR. Structure-function relationships of the G domain, a canonical switch motif. Annu Rev Biochem. 2011;80:943–71.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Wong CH, Chan H, Ho CY, Lai SK, Chan KS, Koh CG, Li HY. Apoptotic histone modification inhibits nuclear transport by regulating RCC1. Nat Cell Biol. 2009;11:36–45.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Yudin D, Fainzilber M. Ran on tracks–cytoplasmic roles for a nuclear regulator. J Cell Sci. 2009;122:587–93.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Zhang C, Clarke PR. Chromatin-independent nuclear envelope assembly induced by Ran GTPase in Xenopus egg extracts. Science. 2000;288:1429–32.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Institut de Biologie Structurale Jean-Pierre Ebel, UMR 5075 (CEA/CNRS/Université Joseph Fourier)GrenobleFrance