Karyopherins and nuclear import.

Proteins of the karyopherin alpha and karyopherin beta families play a central role in nucleocytoplasmic transport. Recently, crystal structures of karyopherin alpha and its complexes with nuclear localization signal peptides, a karyopherin beta2-Ran complex and complexes of full-length and fragments of karyopherin beta1 with import substrates, Ran and nucleoporins have been solved. These karyopherin structures provide valuable insights into understanding the molecular mechanism of nuclear import, especially substrate recognition, substrate release by GTPase and interactions with the nuclear pore complex.

[1]  T. Tsukihara,et al.  The adoption of a twisted structure of importin-beta is essential for the protein-protein interaction required for nuclear transport. , 2000, Journal of molecular biology.

[2]  Sven Berg,et al.  A repeating amino acid motif shared by proteins with diverse cellular roles , 1994, Cell.

[3]  B. Kobe,et al.  Structural basis of recognition of monopartite and bipartite nuclear localization sequences by mammalian importin-alpha. , 2000, Journal of molecular biology.

[4]  G. Blobel,et al.  Nuclear Import of the TATA-binding Protein: Mediation by the Karyopherin Kap114p and a Possible Mechanism for Intranuclear Targeting , 1999, The Journal of cell biology.

[5]  B. Chait,et al.  The Yeast Nuclear Pore Complex: Composition, Architecture, and Transport Mechanism , 2000 .

[6]  K Ribbeck,et al.  Kinetic analysis of translocation through nuclear pore complexes , 2001, The EMBO journal.

[7]  G. Blobel,et al.  Crystallographic Analysis of the Recognition of a Nuclear Localization Signal by the Nuclear Import Factor Karyopherin α , 1998, Cell.

[8]  Peer Bork,et al.  HEAT repeats in the Huntington's disease protein , 1995, Nature Genetics.

[9]  I. Macara,et al.  Importin‐11, a nuclear import receptor for the ubiquitin‐conjugating enzyme, UbcM2 , 2000, The EMBO journal.

[10]  G. Lipowsky,et al.  Exportin 4: a mediator of a novel nuclear export pathway in higher eukaryotes , 2000, The EMBO journal.

[11]  C. Müller,et al.  Structure of importin-β bound to the IBB domain of importin-α , 1999, Nature.

[12]  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.

[13]  S. Kuge,et al.  Nuclear Import of the Yeast AP-1-like Transcription Factor Yap1p Is Mediated by Transport Receptor Pse1p, and This Import Step Is Not Affected by Oxidative Stress* , 2001, The Journal of Biological Chemistry.

[14]  C. Jacq,et al.  Pse1/Kap121‐dependent nuclear localization of the major yeast multidrug resistance (MDR) transcription factor Pdr1 , 2001, Molecular microbiology.

[15]  R. Truant,et al.  Nuclear Import of Cdk/Cyclin Complexes: Identification of Distinct Mechanisms for Import of Cdk2/Cyclin E and Cdc2/Cyclin B1 , 1999, The Journal of cell biology.

[16]  U. Kutay,et al.  The C-terminal domain of TAP interacts with the nuclear pore complex and promotes export of specific CTE-bearing RNA substrates. , 2000, RNA.

[17]  Mark Johnston,et al.  The nuclear exportin Msn5 is required for nuclear export of the Mig1 glucose repressor of Saccharomyces cerevisiae , 1999, Current Biology.

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

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

[20]  G. Blobel,et al.  Structure of the nuclear transport complex karyopherin-β2–Ran˙GppNHp , 1999, Nature.

[21]  F. Bischoff,et al.  The importin β/importin 7 heterodimer is a functional nuclear import receptor for histone H1 , 1999, The EMBO journal.

[22]  F. Bischoff.  Human RanGTPase activating protein RanGAP1 is a homolog of yeast RNA1p involved in messenger RNA processing and transport , 1995 .

[23]  G. Blobel,et al.  The binding site of karyopherin alpha for karyopherin beta overlaps with a nuclear localization sequence. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[24]  William I. Weis,et al.  Three-Dimensional Structure of the Armadillo Repeat Region of β-Catenin , 1997, Cell.

[25]  G. Blobel.  Unidirectional and bidirectional protein traffic across membranes. , 1995, Cold Spring Harbor symposia on quantitative biology.

[26]  Yixian Zheng,et al.  Role of Importin-β in Coupling Ran to Downstream Targets in Microtubule Assembly , 2001, Science.

[27]  Bryan R. Cullen,et al.  Determination of the Functional Domain Organization of the Importin α Nuclear Import Factor , 1998, The Journal of cell biology.

[28]  G. Dreyfuss,et al.  Nup153 is an M9‐containing mobile nucleoporin with a novel Ran‐binding domain , 1999, The EMBO journal.

[29]  G. Blobel,et al.  Two distinct classes of Ran-binding sites on the nucleoporin Nup-358. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

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

[31]  G. Blobel,et al.  The Nucleoporin Nup98 Is a Site for GDP/GTP Exchange on Ran and Termination of Karyopherin β2-mediated Nuclear Import* , 2000, The Journal of Biological Chemistry.

[32]  Karsten Weis,et al.  Importin β Is a Mitotic Target of the Small GTPase Ran in Spindle Assembly , 2001, Cell.

[33]  R. Laskey,et al.  Nuclear targeting sequences--a consensus? , 1991, Trends in biochemical sciences.

[34]  M. Peter,et al.  Nuclear export of Far1p in response to pheromones requires the export receptor Msn5p/Ste21p. , 1999, Genes & development.

[35]  G. Blobel,et al.  The Karyopherin Kap122p/Pdr6p Imports Both Subunits of the Transcription Factor Iia into the Nucleus , 1999, The Journal of cell biology.

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

[37]  L. Gerace,et al.  Gradient of Increasing Affinity of Importin β for Nucleoporins along the Pathway of Nuclear Import , 2001, The Journal of cell biology.

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

[39]  F. Bischoff,et al.  Catalysis of guanine nucleotide exchange of Ran by RCC1 and stimulation of hydrolysis of Ran-bound GTP by Ran-GAP1. , 1995, Methods in enzymology.

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

[41]  E. O’Shea,et al.  Phosphorylation regulates association of the transcription factor Pho4 with its import receptor Pse1/Kap121. , 1998, Genes & development.

[42]  Richard Bayliss,et al.  Structural Basis for the Interaction between FxFG Nucleoporin Repeats and Importin-β in Nuclear Trafficking , 2000, Cell.

[43]  G. Blobel,et al.  The nucleoporin Nup98 associates with the intranuclear filamentous protein network of TPR , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[44]  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.

[45]  T. Martin,et al.  Importin β Recognizes Parathyroid Hormone-related Protein with High Affinity and Mediates Its Nuclear Import in the Absence of Importin α* , 1999, The Journal of Biological Chemistry.

[46]  C. Akey.  Structural plasticity of the nuclear pore complex. , 1995, Journal of molecular biology.

[47]  B. Kobe.  Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin α , 1999, Nature Structural Biology.

[48]  C. Akey,et al.  Three-dimensional architecture of the isolated yeast nuclear pore complex: functional and evolutionary implications. , 1998, Molecular cell.

[49]  E. O’Shea,et al.  The receptor Msn5 exports the phosphorylated transcription factor Pho4 out of the nucleus , 1998, Nature.

[50]  C. Müller,et al.  Nuclear import factors importin α and importin β undergo mutually induced conformational changes upon association , 2000 .

[51]  Catherine G. Takizawa,et al.  Ran-independent nuclear import of cyclin B1-Cdc2 by importin beta. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[52]  G. Blobel,et al.  Nup358, a Cytoplasmically Exposed Nucleoporin with Peptide Repeats, Ran-GTP Binding Sites, Zinc Fingers, a Cyclophilin A Homologous Domain, and a Leucine-rich Region (*) , 1995, The Journal of Biological Chemistry.

[53]  G. Blobel,et al.  Nuclear Import of Spo12p, a Protein Essential for Meiosis* , 2001, The Journal of Biological Chemistry.

[54]  Cynthia J. Brame,et al.  Nuclear Import of Histone H2a and H2b Is Mediated by a Network of Karyopherins , 2001, The Journal of cell biology.

[55]  B. Cullen,et al.  Nuclear import of hnRNP A1 is mediated by a novel cellular cofactor related to karyopherin-beta. , 1997, Journal of cell science.

[56]  G. Blobel,et al.  The peptide repeat domain of nucleoporin Nup98 functions as a docking site in transport across the nuclear pore complex , 1995, Cell.

[57]  Alfred Wittinghofer,et al.  Structural View of the Ran–Importin β Interaction at 2.3 Å Resolution , 1999, Cell.

[58]  M. Hodel,et al.  Quantitative analysis of nuclear localization signal (NLS)-importin alpha interaction through fluorescence depolarization. Evidence for auto-inhibitory regulation of NLS binding. , 2000, The Journal of biological chemistry.

[59]  J Kuriyan,et al.  Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin alpha. , 2000, Structure.

[60]  I. Vernos,et al.  Ran Induces Spindle Assembly by Reversing the Inhibitory Effect of Importin α on TPX2 Activity , 2001, Cell.

[61]  G. Blobel,et al.  The Karyopherin Kap142p/Msn5p Mediates Nuclear Import and Nuclear Export of Different Cargo Proteins , 2001, The Journal of cell biology.

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

[63]  J. Aitchison,et al.  Kap104p-mediated Nuclear Import , 1999, The Journal of Biological Chemistry.

[64]  Mitsuo Sekine,et al.  Snurportin1, an m3G‐cap‐specific nuclear import receptor with a novel domain structure , 1998, The EMBO journal.

[65]  D. Goldfarb,et al.  Evolutionary specialization of the nuclear targeting apparatus. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[66]  F. Bischoff,et al.  Identification of Two Novel RanGTP-binding Proteins Belonging to the Importin β Superfamily* , 2000, The Journal of Biological Chemistry.

[67]  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.