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...
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References
Arnaoutov A, Dasso M. Ran-GTP regulates kinetochore attachment in somatic cells. Cell Cycle. 2005;4:1161–5.
Budhu AS, Wang XW. Loading and unloading: orchestrating centrosome duplication and spindle assembly by Ran/Crm1. Cell Cycle. 2005;4:1510–4.
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.
Clarke PR, Zhang C. Spatial and temporal coordination of mitosis by Ran GTPase. Nat Rev Mol Cell Biol. 2008;9:464–77.
Cook AG, Conti E. Nuclear export complexes in the frame. Curr Opin Struct Biol. 2010;20:247–52.
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.
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.
Fried H, Kutay U. Nucleocytoplasmic transport: taking an inventory. Cell Mol Life Sci. 2003;60:1659–88.
Gruss OJ, Vernos I. The mechanism of spindle assembly: functions of Ran and its target TPX2. J Cell Biol. 2004;166:949–55.
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.
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.
Moore MS, Blobel G. The GTP-binding protein Ran/TC4 is required for protein import into the nucleus. Nature. 1993;365:661–3.
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.
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.
Stewart M. Molecular mechanism of the nuclear protein import cycle. Nat Rev Mol Cell Biol. 2007;8:195–208.
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.
Wittinghofer A, Vetter IR. Structure-function relationships of the G domain, a canonical switch motif. Annu Rev Biochem. 2011;80:943–71.
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.
Yudin D, Fainzilber M. Ran on tracks–cytoplasmic roles for a nuclear regulator. J Cell Sci. 2009;122:587–93.
Zhang C, Clarke PR. Chromatin-independent nuclear envelope assembly induced by Ran GTPase in Xenopus egg extracts. Science. 2000;288:1429–32.
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Petosa, C. (2018). Ran. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_641
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DOI: https://doi.org/10.1007/978-3-319-67199-4_641
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