Ran and Nuclear Transport*

The last several years have witnessed an explosion in our understanding of how proteins and RNAs traffic into and out of the nucleus. Although an increasing number of proteins have been implicated in different nuclear transport pathways, the small GTPase Ran appears to play a central role in coordinating and driving much of this nuclear traffic. Recently there have been several excellent reviews describing the multiple pathways of nuclear transport (1–5); consequently this review will focus on what is currently known about Ran and its biochemical properties and what is presently understood of the role of the Ran GTPase cycle during nuclear transport.

[1]  C. Feldherr,et al.  The nuclear import factor p10 regulates the functional size of the nuclear pore complex during oogenesis. , 1998, Journal of cell science.

[2]  G. Blobel,et al.  Transport routes through the nuclear pore complex. , 1998, Current opinion in cell biology.

[3]  Alfred Wittinghofer,et al.  The 1.7 Å crystal structure of the regulator of chromosome condensation (RCC1) reveals a seven-bladed propeller , 1998, Nature.

[4]  E. Pennisi.  The Nucleus's Revolving Door , 1998, Science.

[5]  M. Fornerod,et al.  Nucleocytoplasmic Transport: The Last 200 Nanometers , 1998, Cell.

[6]  G. Lipowsky,et al.  Identification of a tRNA-specific nuclear export receptor. , 1998, Molecular cell.

[7]  G. Dreyfuss,et al.  Import and export of the nuclear protein import receptor transportin by a mechanism independent of GTP hydrolysis , 1998, Current Biology.

[8]  G. Blobel,et al.  A Distinct and Parallel Pathway for the Nuclear Import of an mRNA-binding Protein , 1997, The Journal of cell biology.

[9]  G. Blobel,et al.  A Nuclear Import Pathway for a Protein Involved in tRNA Maturation , 1997, The Journal of cell biology.

[10]  Dirk Görlich,et al.  RanBP1 is crucial for the release of RanGTP from importin β‐related nuclear transport factors , 1997, FEBS letters.

[11]  Minoru Yoshida,et al.  CRM1 is responsible for intracellular transport mediated by the nuclear export signal , 1997, Nature.

[12]  U. Kutay,et al.  The asymmetric distribution of the constituents of the Ran system is essential for transport into and out of the nucleus , 1997, The EMBO journal.

[13]  Elena Smirnova,et al.  Yrb4p, a yeast Ran–GTP‐binding protein involved in import of ribosomal protein L25 into the nucleus , 1997, The EMBO journal.

[14]  C. Dargemont,et al.  Evidence for a role of CRM1 in signal-mediated nuclear protein export. , 1997, Science.

[15]  F. Bischoff,et al.  Export of Importin α from the Nucleus Is Mediated by a Specific Nuclear Transport Factor , 1997, Cell.

[16]  Minoru Yoshida,et al.  CRM1 Is an Export Receptor for Leucine-Rich Nuclear Export Signals , 1997, Cell.

[17]  Karsten Weis,et al.  Exportin 1 (Crm1p) Is an Essential Nuclear Export Factor , 1997, Cell.

[18]  G. Blobel,et al.  Disassembly of RanGTP-Karyopherin β Complex, an Intermediate in Nuclear Protein Import* , 1997, The Journal of Biological Chemistry.

[19]  P. Bork,et al.  A Novel Class of RanGTP Binding Proteins , 1997, The Journal of cell biology.

[20]  I. Macara,et al.  Requirement of guanosine triphosphate-bound ran for signal-mediated nuclear protein export. , 1997, Science.

[21]  P. Silver,et al.  Nucleocytoplasmic transport of macromolecules , 1997, Microbiology and molecular biology reviews : MMBR.

[22]  G. Blobel,et al.  A Distinct Nuclear Import Pathway Used by Ribosomal Proteins , 1997, Cell.

[23]  G. Blobel,et al.  Karyopherin beta2 mediates nuclear import of a mRNA binding protein. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Erich A. Nigg,et al.  Nucleocytoplasmic transport: signals, mechanisms and regulation , 1997, Nature.

[25]  M. Fornerod,et al.  The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88 , 1997, The EMBO journal.

[26]  F. Melchior,et al.  A Small Ubiquitin-Related Polypeptide Involved in Targeting RanGAP1 to Nuclear Pore Complex Protein RanBP2 , 1997, Cell.

[27]  I. Macara,et al.  Mutations within the Ran/TC4 GTPase , 1996, The Journal of Biological Chemistry.

[28]  G. Blobel,et al.  A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase-activating protein RanGAP1 between the cytosol and the nuclear pore complex , 1996, The Journal of cell biology.

[29]  A. Lamond,et al.  Characterization of the nuclear protein import mechanism using Ran mutants with altered nucleotide binding specificities. , 1996, The EMBO journal.

[30]  S. Adam,et al.  RanBP1 stabilizes the interaction of Ran with p97 nuclear protein import , 1996, The Journal of cell biology.

[31]  G. Blobel,et al.  Kap104p: A Karyopherin Involved in the Nuclear Transport of Messenger RNA Binding Proteins , 1996, Science.

[32]  F. Bischoff,et al.  Identification of different roles for RanGDP and RanGTP in nuclear protein import. , 1996, The EMBO journal.

[33]  G. Dreyfuss,et al.  A Novel Receptor-Mediated Nuclear Protein Import Pathway , 1996, Cell.

[34]  P. Silver,et al.  The NTF2 Gene Encodes an Essential, Highly Conserved Protein That Functions in Nuclear Transport in Vivo* , 1996, The Journal of Biological Chemistry.

[35]  T. Nishimoto,et al.  RCC1 in the Ran pathway. , 1996, Journal of biochemistry.

[36]  A. Hopper,et al.  Nucleus-associated pools of Rna1p, the Saccharomyces cerevisiae Ran/TC4 GTPse activating protein involved in nucleus/cytosol transit. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[37]  E. Kiseleva,et al.  RNP export is mediated by structural reorganization of the nuclear pore basket. , 1996, Journal of molecular biology.

[38]  D. Jans,et al.  Regulation of protein transport to the nucleus: central role of phosphorylation. , 1996, Physiological reviews.

[39]  A. Hopper,et al.  Regulation of mRNA export in response to stress in Saccharomyces cerevisiae. , 1996, Genes & development.

[40]  L. Gerace,et al.  A GTPase distinct from Ran is involved in nuclear protein import , 1996, The Journal of cell biology.

[41]  G. Blobel,et al.  Role of the Nuclear Transport Factor p10 in Nuclear Import , 1996, Science.

[42]  P. D’Eustachio,et al.  The small nuclear GTPase Ran: How much does it run? , 1996, BioEssays : news and reviews in molecular, cellular and developmental biology.

[43]  G. Blobel,et al.  Protein import into nuclei: association and dissociation reactions involving transport substrate, transport factors, and nucleoporins , 1995, Cell.

[44]  E. Hartmann,et al.  Distinct functions for the two importin subunits in nuclear protein import , 1995, Nature.

[45]  G. Blobel,et al.  Identification of a Yeast Karyopherin Heterodimer That Targets Import Substrate to Mammalian Nuclear Pore Complexes (*) , 1995, The Journal of Biological Chemistry.

[46]  G. Blobel,et al.  Mammalian karyopherin alpha 1 beta and alpha 2 beta heterodimers: alpha 1 or alpha 2 subunit binds nuclear localization signal and beta subunit interacts with peptide repeat-containing nucleoporins. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[47]  S. Adam,et al.  Sequence and characterization of cytoplasmic nuclear protein import factor p97 , 1995, The Journal of cell biology.

[48]  I. Macara,et al.  The C Terminus of the Nuclear RAN/TC4 GTPase Stabilizes the GDP-bound State and Mediates Interactions with RCC1, RAN-GAP, and HTF9A/RANBP1 (*) , 1995, The Journal of Biological Chemistry.

[49]  A. Lamond,et al.  Identification of hSRP1 alpha as a functional receptor for nuclear localization sequences. , 1995, Science.

[50]  B. Paschal,et al.  Identification of NTF2, a cytosolic factor for nuclear import that interacts with nuclear pore complex protein p62 , 1995, The Journal of cell biology.

[51]  R. Kraft,et al.  Two different subunits of importin cooperate to recognize nuclear localization signals and bind them to the nuclear envelope , 1995, Current Biology.

[52]  W. Kabsch,et al.  Crystal structure of the nuclear Ras-related protein Ran in its GDP-bound form , 1995, Nature.

[53]  G. Blobel,et al.  Previously identified protein of uncertain function is karyopherin alpha and together with karyopherin beta docks import substrate at nuclear pore complexes. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[54]  G. Blobel,et al.  Identification of a protein complex that is required for nuclear protein import and mediates docking of import substrate to distinct nucleoporins. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[55]  F. Bischoff,et al.  Human RanGTPase-activating protein RanGAP1 is a homologue of yeast Rna1p involved in mRNA processing and transport. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[56]  F. Bischoff,et al.  Co‐activation of RanGTPase and inhibition of GTP dissociation by Ran‐GTP binding protein RanBP1. , 1995, The EMBO journal.

[57]  F. Bischoff,et al.  Interaction of the nuclear GTP-binding protein Ran with its regulatory proteins RCC1 and RanGAP1. , 1995, Biochemistry.

[58]  E. Hartmann,et al.  Isolation of a protein that is essential for the first step of nuclear protein import , 1994, Cell.

[59]  G. Blobel,et al.  Purification of a Ran-interacting protein that is required for protein import into the nucleus. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[60]  T. Mcclanahan,et al.  Ligand for FLT3/FLK2 receptor tyrosine kinase regulates growth of haematopoietic stem cells and is encoded by variant RNAs , 1994, Nature.

[61]  C. Feldherr,et al.  Role of nuclear trafficking in regulating cellular activity. , 1994, International review of cytology.

[62]  Mark S. Boguski,et al.  Proteins regulating Ras and its relatives , 1993, Nature.

[63]  F. Melchior,et al.  Inhibition of nuclear protein import by nonhydrolyzable analogues of GTP and identification of the small GTPase Ran/TC4 as an essential transport factor [published erratum appears in J Cell Biol 1994 Jan;124(1-2):217] , 1993, The Journal of cell biology.

[64]  G. Blobel,et al.  The GTP-binding protein Ran/TC4 is required for protein import into the nucleus , 1993, Nature.

[65]  F. Bischoff,et al.  Mitotic regulator protein RCC1 is complexed with a nuclear ras-related polypeptide. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[66]  S. Adam,et al.  Cytosolic proteins that specifically bind nuclear location signals are receptors for nuclear import , 1991, Cell.

[67]  P. D’Eustachio,et al.  Characterization of four novel ras-like genes expressed in a human teratocarcinoma cell line , 1990, Molecular and cellular biology.

[68]  D. Newmeyer,et al.  Nuclear import can be separated into distinct steps in vitro: Nuclear pore binding and translocation , 1988, Cell.

[69]  W. Richardson,et al.  Nuclear protein migration involves two steps: Rapid binding at the nuclear envelope followed by slower translocation through nuclear pores , 1988, Cell.