Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
EMBO J
1997 Mar 17;166:1153-63. doi: 10.1093/emboj/16.6.1153.
Show Gene links
Show Anatomy links
Dominant-negative mutants of importin-beta block multiple pathways of import and export through the nuclear pore complex.
Kutay U, Izaurralde E, Bischoff FR, Mattaj IW, Görlich D.
???displayArticle.abstract???
Nuclear protein import proceeds through the nuclear pore complex (NPC). Importin-beta mediates translocation via direct interaction with NPC components and carries importin-alpha with the NLS substrate from the cytoplasm into the nucleus. The import reaction is terminated by the direct binding of nuclear RanGTP to importin-beta which dissociates the importin heterodimer. Here, we analyse the sites of interaction on importin-beta for its multiple partners. Ran and importin-alpha respectively require residues 1-364 and 331-876 of importin-beta for binding. Thus, RanGTP-mediated release of importin-alpha from importin-beta is likely to be an active displacement rather than due to simple competition between Ran and importin-alpha for a common binding site. Importin-beta has at least two non-overlapping sites of interaction with the NPC, which could potentially be used sequentially during translocation. Our data also suggest that termination of import involves a transient release of importin-beta from the NPC. Importin-beta fragments which bind to the NPC, but not to Ran, resist this release mechanism. As would be predicted from this, these importin-beta mutants are very efficient inhibitors of NLS-dependent protein import. Surprisingly, however, they also inhibit M9 signal-mediated nuclear import as well as nuclear export of mRNA, U snRNA, and the NES-containing Rev protein. This suggests that mediators of these various transport events share binding sites on the NPC and/or that mechanisms exist to coordinate translocation through the NPC via different nucleocytoplasmic transport pathways.
Adam,
Cytosolic proteins that specifically bind nuclear location signals are receptors for nuclear import.
1991, Pubmed
Adam,
Cytosolic proteins that specifically bind nuclear location signals are receptors for nuclear import.
1991,
Pubmed Bischoff,
Human RanGTPase-activating protein RanGAP1 is a homologue of yeast Rna1p involved in mRNA processing and transport.
1995,
Pubmed Bischoff,
RanGAP1 induces GTPase activity of nuclear Ras-related Ran.
1994,
Pubmed Chi,
Sequence and characterization of cytoplasmic nuclear protein import factor p97.
1995,
Pubmed Corbett,
Rna1p, a Ran/TC4 GTPase activating protein, is required for nuclear import.
1995,
Pubmed Coutavas,
Characterization of proteins that interact with the cell-cycle regulatory protein Ran/TC4.
1993,
Pubmed
,
Xenbase Dingwall,
Nuclear targeting sequences--a consensus?
1991,
Pubmed Edelhoch,
Spectroscopic determination of tryptophan and tyrosine in proteins.
1967,
Pubmed Feldherr,
Movement of a karyophilic protein through the nuclear pores of oocytes.
1984,
Pubmed
,
Xenbase Fischer,
The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs.
1995,
Pubmed Floer,
The nuclear transport factor karyopherin beta binds stoichiometrically to Ran-GTP and inhibits the Ran GTPase activating protein.
1996,
Pubmed Gerace,
Nuclear export signals and the fast track to the cytoplasm.
1995,
Pubmed Görlich,
Two different subunits of importin cooperate to recognize nuclear localization signals and bind them to the nuclear envelope.
1995,
Pubmed
,
Xenbase Görlich,
Identification of different roles for RanGDP and RanGTP in nuclear protein import.
1996,
Pubmed
,
Xenbase Görlich,
Distinct functions for the two importin subunits in nuclear protein import.
1995,
Pubmed
,
Xenbase Görlich,
Importin provides a link between nuclear protein import and U snRNA export.
1996,
Pubmed
,
Xenbase Görlich,
Isolation of a protein that is essential for the first step of nuclear protein import.
1994,
Pubmed
,
Xenbase Görlich,
A 41 amino acid motif in importin-alpha confers binding to importin-beta and hence transit into the nucleus.
1996,
Pubmed
,
Xenbase Görlich,
Nucleocytoplasmic transport.
1996,
Pubmed Guddat,
Protein-mediated nuclear export of RNA: 5S rRNA containing small RNPs in xenopus oocytes.
1990,
Pubmed
,
Xenbase Hopper,
The yeast RNA1 gene product necessary for RNA processing is located in the cytosol and apparently excluded from the nucleus.
1990,
Pubmed Imamoto,
A karyophilic protein forms a stable complex with cytoplasmic components prior to nuclear pore binding.
1995,
Pubmed Imamoto,
In vivo evidence for involvement of a 58 kDa component of nuclear pore-targeting complex in nuclear protein import.
1995,
Pubmed
,
Xenbase Izaurralde,
RNA export.
1995,
Pubmed Jarmolowski,
Nuclear export of different classes of RNA is mediated by specific factors.
1994,
Pubmed
,
Xenbase Klebe,
Interaction of the nuclear GTP-binding protein Ran with its regulatory proteins RCC1 and RanGAP1.
1995,
Pubmed
,
Xenbase Lounsbury,
Ran binding domains promote the interaction of Ran with p97/beta-karyopherin, linking the docking and translocation steps of nuclear import.
1996,
Pubmed Meier,
Nucleotide sequence of two mouse histone H4 genes.
1989,
Pubmed Melchior,
Inhibition of nuclear protein import by nonhydrolyzable analogues of GTP and identification of the small GTPase Ran/TC4 as an essential transport factor.
1993,
Pubmed Melchior,
A functional homologue of the RNA1 gene product in Schizosaccharomyces pombe: purification, biochemical characterization, and identification of a leucine-rich repeat motif.
1993,
Pubmed Michael,
A nuclear export signal in hnRNP A1: a signal-mediated, temperature-dependent nuclear protein export pathway.
1995,
Pubmed Moore,
The GTP-binding protein Ran/TC4 is required for protein import into the nucleus.
1993,
Pubmed
,
Xenbase Moore,
The two steps of nuclear import, targeting to the nuclear envelope and translocation through the nuclear pore, require different cytosolic factors.
1992,
Pubmed
,
Xenbase Moore,
Purification of a Ran-interacting protein that is required for protein import into the nucleus.
1994,
Pubmed
,
Xenbase Moroianu,
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,
Pubmed Moroianu,
Nuclear protein import: Ran-GTP dissociates the karyopherin alphabeta heterodimer by displacing alpha from an overlapping binding site on beta.
1996,
Pubmed Ohtsubo,
The RCC1 protein, a regulator for the onset of chromosome condensation locates in the nucleus and binds to DNA.
1989,
Pubmed Panté,
Sequential binding of import ligands to distinct nucleopore regions during their nuclear import.
1996,
Pubmed
,
Xenbase Paschal,
Identification of NTF2, a cytosolic factor for nuclear import that interacts with nuclear pore complex protein p62.
1995,
Pubmed Piñol-Roma,
hnRNP proteins: localization and transport between the nucleus and the cytoplasm.
1993,
Pubmed Pokrywka,
Nuclear export pathways of tRNA and 40 S ribosomes include both common and specific intermediates.
1995,
Pubmed
,
Xenbase Pollard,
A novel receptor-mediated nuclear protein import pathway.
1996,
Pubmed Radu,
Identification of a protein complex that is required for nuclear protein import and mediates docking of import substrate to distinct nucleoporins.
1995,
Pubmed
,
Xenbase Rexach,
Protein import into nuclei: association and dissociation reactions involving transport substrate, transport factors, and nucleoporins.
1995,
Pubmed Schlenstedt,
Mutants in a yeast Ran binding protein are defective in nuclear transport.
1995,
Pubmed Weis,
Identification of hSRP1 alpha as a functional receptor for nuclear localization sequences.
1995,
Pubmed Weis,
The conserved amino-terminal domain of hSRP1 alpha is essential for nuclear protein import.
1996,
Pubmed Wen,
Identification of a signal for rapid export of proteins from the nucleus.
1995,
Pubmed
