SEARCH · PubMed Health

Results for “Nuclear Localization Signals”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,027 records · Page 57Linked to original sources

PubMed2000

Characterization of CMF1 in avian skeletal muscle.

This study reports the identification of the CMF1 protein in somites and embryonic limb muscle. We have previously described CMF1 in developing cardiac muscle. CMF1 is a member of the LEK family of proteins, which are involved in regulating mitosis. Our current data suggest that CMF1 expressed in skeletal and cardiac myocytes is the product of a single gene and that the two proteins are homologous or very highly conserved. Immunohistochemistry shows a dynamic subcellular localization of CMF1 in differentiating skeletal myoblasts: Early myoblasts stain positively for CMF1 antigen in the nucleus, while differentiating myoblasts stain positively in the cytoplasm. CMF1 expression precedes myosin. Later, CMF1 and myosin are detected in the cytoplasm of the same cells. Transfection analysis identifies a functional nuclear localization signal (NLS) in CMF1, whose nuclear transport capability is modified by external sequences. To characterize the function of CMF1 in skeletal muscle, we used antisense oligonucleotides to disrupt CMF1 in myoblast cultures. Expression of CMF1 in early myotubes is reduced by an average of 40% on a cell by cell basis, with a 56% reduction in anti-myosin staining. These data suggest that CMF1 is involved in induction and/or accumulation of myosin in differentiating myocytes.

Amino Acid Sequence↗

PubMed2005

Nuclear condensation of cyclic adenosine monophosphate responsive element-binding protein in discrete murine brain structures.

We have directed a polyclonal antibody against an oligo-peptide (123-136) of the transcription factor cyclic AMP responsive element-binding protein (CREB) including the serine residue at 133. Rabbit sera were purified by ammonium sulfate precipitation, followed by affinity chromatography to homogeneity on one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. The purified antibody not only induced marked supershift of CREB binding, without affecting binding of activator protein-1 on gel retardation electrophoresis, but also differentiated between CREB and CREB phosphorylated at serine133 in brain nuclear fractions on Western blotting. Immunoreactive CREB was detected in both cytosolic and nuclear fractions of discrete murine brain structures but was more highly condensed in cerebellum than in neocortex and hippocampus. Incubation of brain nuclear fractions led to a marked export of immunoreactive CREB in a temperature-dependent manner, whereas the temperature-dependent export activity was significantly lower in cerebellum than in other brain structures. Suppression of general new protein synthesis by cycloheximide (500 mg/kg, i.p.) in vivo resulted in a significant decrease in the nuclear CREB level, with a concomitant increase in the cytosolic level in hippocampus, but not in cerebellum. These results suggest that the nuclear export activity might vary from region to region in murine brains through a hitherto unidentified mechanism other than the nuclear localization signal, to result in different nuclear condensation ratios for subsequent elicitation of differential transcriptional activities by the constitutive transcription factor CREB in the nucleus.

Active Transport, Cell Nucleus↗

PubMed2002

E2F sites that can interact with E2F proteins cloned from rice are required for meristematic tissue-specific expression of rice and tobacco proliferating cell nuclear antigen promoters.

Plants have recently been found to have E2F-like and Rb-like proteins, regulators responsible for the G1(G0)-S phase transition of the cell cycle in animals. Here we show that E2F is involved in transcription of plant genes for proliferating cell nuclear antigen (PCNA), which is required for DNA replication. Potential E2F binding sites found in the rice PCNA promoters mediated transcriptional activation in actively dividing cells and tissues of tobacco, but not transcriptional repression in terminally differentiated tissues, as also observed for the PCF binding sites previously found in the rice promoter. Similar results were obtained from analyses for a PCNA promoter isolated from tobacco, which contained two E2F-like sites, each with a different degree of contribution to the promoter activation. These E2F-like sites except for a rice site were indeed bound specifically by recombinant proteins of rice E2F, OsE2F1 and OsE2F2, and complexes of OsE2F1 with Arabidopsis DP proteins. Furthermore, OsE2F1 had the ability to transactivate an E2F-reporter gene containing the tobacco E2F site on co-expression with an Arabidopsis DP, and the transactivation was greatly enhanced by tagging a canonical nuclear localization signal to OsE2F1, suggesting a nuclear import-mediated regulation of the OsE2F1 function. In addition, we found that a large number of replication- and mismatch repair-associated genes in Arabidopsis contain E2F binding sequences conserved in their predicted promoter regions.

Amino Acid Sequence↗

PubMed2001

The trophinin gene encodes a novel group of MAGE proteins, magphinins, and regulates cell proliferation during gametogenesis in the mouse.

Trophinin is a membrane protein that mediates apical cell adhesion between trophoblastic cells and luminal epithelial cells of the endometrium and is implicated in the initial attachment during the process of human embryo implantation. The present study identified novel trophinin gene transcripts, which encode proteins structurally distinct from trophinin protein in the mouse. We designated these proteins "magphinins," because they share consensus amino acid sequences with MAGE (melanoma-associated antigen) superfamily proteins. Among many MAGE proteins, magphinins are closely related to NRAGE, which mediates p75 neurotrophin receptor-dependent apoptosis, and necdin, which is a strong suppressor of cell proliferation in post-mitotic neurons. There are three major forms of magphinins, i.e. magphinin-alpha, -beta, and -gamma, in the mouse, which are formed due to alternative usage of different exons. Northern blot analysis revealed that magphinins are expressed in brain, ovary, testis, and epididymis. In addition, Western blot analysis and in vitro translation experiments showed that magphinins expressed in the mouse ovary and testis are translation products utilizing the second initiation AUG codon and contain an active nuclear localization signal. Ectopic expression of magphinins in mammalian cells resulted in nuclear localization of magphinin and suppressed cell proliferation. Immunohistochemistry of the mouse ovary and testis showed that magphinin proteins are distributed in the cytoplasm of the male and female germ cells, whereas these proteins are translocated to the nucleus at a specific stage of gametogenesis. These results strongly suggest that magphinins regulate cell proliferation during gametogenesis in the mouse.

Alternative Splicing↗

PubMed2000

An ATP-dependent, Ran-independent mechanism for nuclear import of the U1A and U2B" spliceosome proteins.

Nuclear import of the two uracil-rich small nuclear ribonucleoprotein (U snRNP) components U1A and U2B" is mediated by unusually long and complex nuclear localization signals (NLSs). Here we investigate nuclear import of U1A and U2B" in vitro and demonstrate that it occurs by an active, saturable process. Several lines of evidence suggest that import of the two proteins occurs by an import mechanism different to those characterized previously. No cross competition is seen with a variety of previously studied NLSs. In contrast to import mediated by members of the importin-beta family of nucleocytoplasmic transport receptors, U1A/U2B" import is not inhibited by either nonhydrolyzable guanosine triphosphate (GTP) analogues or by a mutant of the GTPase Ran that is incapable of GTP hydrolysis. Adenosine triphosphate is capable of supporting U1A and U2B" import, whereas neither nonhydrolyzable adenosine triphosphate analogues nor GTP can do so. U1A and U2B" import in vitro does not require the addition of soluble cytosolic proteins, but a factor or factors required for U1A and U2B" import remains tightly associated with the nuclear fraction of conventionally permeabilized cells. This activity can be solubilized in the presence of elevated MgCl(2). These data suggest that U1A and U2B" import into the nucleus occurs by a hitherto uncharacterized mechanism.

Adenosine Triphosphate↗

PubMed2003

The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization.

The cap-binding eukaryotic initiation factor eIF4E is phosphorylated by the mitogen-activated protein (MAP) kinase-interacting kinases (Mnk's). Three forms of the Mnk's exist in human cells: Mnk1, Mnk2a, and Mnk2b. These last two are derived from the same gene by alternative splicing and differ only at their C termini. While Mnk2a contains a MAP kinase-binding site in this region, Mnk2b lacks such a sequence and is much less readily activated by MAP kinases in vitro. Expression of Mnk2b in mammalian cells leads to increased phosphorylation of eIF4E, showing that it acts as an eIF4E kinase in vivo. While Mnk2a is cytoplasmic, a substantial amount of Mnk2b is found in the nucleus. Both enzymes contain a stretch of basic residues in their N termini that plays a role in binding to eIF4G and functions as a nuclear localization signal. Binding of eIF4G or nuclear import appears to be regulated by the C terminus of Mnk2a. Furthermore, the MAP kinase-binding site of Mnk2a regulates nuclear entry. Within the nucleus, Mnk2b and certain variants of Mnk2a that are present in the nucleus colocalize with the promyelocytic leukemia protein PML, which also binds to eIF4E.

Alternative Splicing↗

PubMed2000

The ubiquitin-dependent proteolytic system and other potential targets for the modulation of nuclear factor-kB (NF-kB).

Nuclear Factor-kB (NF-kB), is a transcription factor composed of dimeric complexes of p50 (NF-kB1) or p52 (NF-kB2) usually associated with members of the Rel family (p65, c-Rel, Rel B) which have potent transactivation domains. Different combinations of NF-kB/Rel proteins bind distinct kB sites to regulate the transcription of different genes. In resting cells NF-kB resides in the cytoplasm in inactive form, complexed to members of a family of inhibitory proteins referred to as IkB. The bound IkB masks the NF-kB nuclear localization signal and thereby inhibits its nuclear transport. NF-kB can be activated by a variety of signals relevant to pathophysiology including inflammatory cytokines and bacterial lipopolysaccharides (LPS) as well as oxidative and fluid mechanical stress. Upon activation by these stimuli, IkB is phosphorylated and subsequently degraded. Phosphorylation targets IkB for ubiquitination and degradation by the 26S proteasome thus leading to NF-kB nuclear translocation. The same proteolytic pathway is involved in the processing of the p105 and p100 precursors to generate mature p50 and p52 subunits, respectively. Once in the nucleus, NF-kB is able to regulate the expression of many genes involved in the immune and inflammatory responses (i.e. inflammatory cytokines and adhesion molecules). Thus, new approaches to modulating NF-kB activation, and as a consequence inflammatory or metastatic processes, may take advantage of the selectivity of the ubiquitination and ATP-dependent proteolytic processes leading to IkB turnover. This review will analyze the current strategies aimed at interfering with NF-kB activation and will consider the ubiquitination system as a new selective target for the development of new anti-inflammatory therapies.

Animals↗

PubMed1995

Axoplasm enriched in a protein mobilized by nerve injury induces memory-like alterations in Aplysia neurons.

Axon regeneration after injury and long-term alterations associated with learning both require protein synthesis in the neuronal cell body, but the signals that initiate these changes are largely unknown. Direct evidence that axonal injury activates molecular signals in the axon was obtained by injecting axoplasm from crushed or uncrushed nerves into somata of sensory neurons with uncrushed axons. Those injected with crush axoplasm behaved as if their axons had been crushed, exhibiting increases in both repetitive firing and spike duration, and a decrease in spike afterhyperpolarization 1 d after injection. Because similar changes occur in the same cells after learning, these data suggest that some of the long-lasting adaptive changes that occur after injury and learning may be induced by common axoplasmic signals. Since the signals in axoplasm must be conveyed to the cell soma, we have begun to test the hypothesis that at least some of these signals are proteins containing a nuclear localization signal (NLS). Axoplasmic proteins at the crush site and those that accumulated at a ligation proximal to the crush were probed with an antibody to an amino acid sequence (sp) containing a NLS that provides access to the retrograde transport/nuclear import pathway. One protein, sp97, displayed properties expected of an axonal injury signal: it responded to injury by undergoing an anterograde-to-retrograde change in movement and, when the ligation was omitted, it was transported to the cell bodies of the injured neurons.

Animals↗

PubMed1996

Dual mechanisms of repression of E2F1 activity by the retinoblastoma gene product.

The retinoblastoma gene product, pRb, negatively regulates cell proliferation by modulating the activity of the transcription factor E2F1 that controls expression of S-phase genes. To dissect transcriptional regulation of E2F1 by pRb, we developed a means to control the subcellular localization of pRb by exchanging its constitutive nuclear localization signal (NLS) with an inducible nuclear targeting domain from the glucocorticoid receptor (GR). In co-transfection experiments in hormone-free media, pRb delta NLS-GR sequestered E2F1 in the cytoplasm; addition of steroid hormones induced co-translocation of pRb delta NLS-GR and E2F1 to the nucleus. A pRb allele lacking a NLS, pRb delta NLS, also sequestered E2F1 in the cytoplasm. Both nuclear and cytoplasmic pRb delta NLS-GR repressed transcription from a simple, E2F1-activated, promoter equally well. pRb delta NLS-GR exerted differential effects on complex promoters containing an activator and E2F sites that acted as either positive or negative elements. We propose a dual mechanism of transcriptional repression by pRb which allows tight control of E2F1-responsive genes: a pRb-E2F1 repressor unit is assembled off DNA to pre-empt transcriptional activation by E2F1; recruitment of this repressor unit to cognate binding sites on promoters allows silencing of adjacent promoter elements.

3T3 Cells↗

PubMed1997

[Nuclear pore-targeting complex/importin family].

Transport of proteins into the nucleus is essential for many cellular functions to proceed. Nuclear import of proteins is directed by short amino acid sequence termed nuclear localization signals (NLS). The process of nuclear import is highly selective, requires energy, and is mediated by several soluble/cytoplasmic factors. At the entry to the import pathway, nuclear proteins form a stable complex, termed nuclear pore-targeting complex (PTAC). The complex consists of a nuclear protein and two cytosolic factors termed PTAC58 (importin alpha) and PTAC97 (importin beta). This report describes the function of PTAC/importin as well as their recently identified family proteins.

Biological Transport↗

PubMed2000

Identification of cDNAs encoding two novel nuclear proteins, IMUP-1 and IMUP-2, upregulated in SV40-immortalized human fibroblasts.

Using a model system of young, senescent and SV40-immortalized WI-38 fibroblasts, we identified two mRNAs upregulated in immortalized cells (imup-1, immortalization-upregulated protein 1, and imup-2). Compared to normal tissues, both genes were more frequently expressed in cancer cells. The open reading frame of imup-1 spans 321bp, coding for a 10.9 kDa protein of 106 amino acids, while an insertion of 59bp in the otherwise identical mRNA of imup-2 leads to a frameshift, resulting in an 8.5 kDa protein of 85 amino acids. Database searches identified these genes on chromosome 19, which could account for the cloned imup-1 and imup-2 transcripts by alternative splicing. Southern blot analysis of digested genomic DNA confirmed that both transcripts are derived from a single locus. The expressed proteins IMUP-1 and IMUP-2 share 46 identical N-terminal amino acids, whereas the C-termini are unrelated. Green fluorescent protein-fusions of both IMUP-1 and IMUP-2 accumulated in the nucleus of HeLa cells. The C-terminus of IMUP-1 contains a bipartite nuclear localization signal, the deletion of which impaired nuclear translocation. In-vitro translated proteins bound to poly(rG), but did not interact with single-stranded DNA or double-stranded DNA. The nuclear localization of IMUP-1 and IMUP-2 as well as the upregulation of both underlying mRNAs in immortalized cells suggest a function in immortalization.

Alternative Splicing↗

PubMed2006

Mutual regulation of c-Jun and ATF2 by transcriptional activation and subcellular localization.

ATF2 and c-Jun are key components of activating protein-1 and function as homodimers or heterodimers. c-Jun-ATF2 heterodimers activate the expression of many target genes, including c-jun, in response to a variety of cellular and environmental signals. Although it has been believed that c-Jun and ATF2 are constitutively localized in the nucleus, where they are phosphorylated and activated by mitogen-activated protein kinases, the molecular mechanisms underlying the regulation of their transcriptional activities remain to be defined. Here we show that ATF2 possesses a nuclear export signal in its leucine zipper region and two nuclear localization signals in its basic region, resulting in continuous shuttling between the cytoplasm and the nucleus. Dimerization with c-Jun in the nucleus prevents the export of ATF2 and is essential for the transcriptional activation of the c-jun promoter. Importantly, c-Jun-dependent nuclear localization of ATF2 occurs during retinoic acid-induced differentiation and UV-induced cell death in F9 cells. Together, these findings demonstrate that ATF2 and c-Jun mutually regulate each other by altering the dynamics of subcellular localization and by positively impacting transcriptional activity.

Activating Transcription Factor 2↗

PubMed2005

Identification of the LEDGF/p75 HIV-1 integrase-interaction domain and NLS reveals NLS-independent chromatin tethering.

To investigate the basis for the LEDGF/p75 dependence of HIV-1 integrase (IN) nuclear localization and chromatin association, we used cell lines made stably deficient in endogenous LEDGF/p75 by RNAi to analyze determinants of its location in cells and its ability to interact with IN. Deletion of C-terminal LEDGF/p75 residues 340-417 preserved nuclear and chromatin localization but abolished the interaction with IN and the tethering of IN to chromatin. Transfer of this IN-binding domain (IBD) was sufficient to confer HIV-1 IN interaction to GFP. HRP-2, the only other human protein with an identifiable IBD domain, was found to translocate IN to the nucleus of LEDGF/p75(-) cells. However, in contrast to LEDGF/p75, HRP-2 is not chromatin bound and does not tether IN to chromatin. A single classical nuclear localization signal (NLS) in the LEDGF/p75 N-terminal region ((146)RRGRKRKAEKQ(156)) was found by deletion mapping and was shown to be transferable to pyruvate kinase. Four central basic residues in the NLS are critical for its activity. Strikingly, however, stable expression studies with NLS(+/-) and IBD(+/-) mutants revealed that the NLS, although responsible for LEDGF/p75 nuclear import, is dispensable for stable, constitutive nuclear association of LEDGF/p75 and IN. Both wild-type LEDGF/p75 and NLS-mutant LEDGF/p75 remain entirely chromatin associated throughout the cell cycle, and each tethers IN to chromatin. Thus, these experiments reveal stable nuclear sequestration of a transcriptional regulator by chromatin during the nuclear-cytosolic mixing of cell division, which additionally enables stable tethering of IN to chromatin. LEDGF/p75 is a multidomain adaptor protein that interacts with the nuclear import apparatus, lentiviral IN proteins and chromatin by means of an NLS, an IBD and additional chromatin-interacting domains.

Active Transport, Cell Nucleus↗

PubMed2000

Regulator of G protein signaling RGS3T is localized to the nucleus and induces apoptosis.

RGS3 belongs to a family of the regulators of G protein signaling (RGS). We previously demonstrated that cytosolic RGS3 translocates to the membrane to inhibit G(q/11) signaling (Dulin, N. O., Sorokin, A., Reed, E., Elliott, S., Kehrl, J., and Dunn, M. J. (1999) Mol. Cell. Biol. 19, 714-723). This study examines the properties of a recently identified truncated variant termed RGS3T. Both RGS3 and RGS3T bound to endogenous Galpha(q/11) and inhibited endothelin-1-stimulated calcium mobilization and mitogen-activated protein kinase activity to a similar extent. However, unlike cytosolically localized RGS3, RGS3T was found predominantly in the nucleus and partially in the plasma membrane. Furthermore, RGS3T, but not RGS3, caused cell rounding and membrane blebbing. Finally, 44% of RGS3T-transfected cells underwent apoptosis after serum withdrawal, which was significantly higher than that of RGS3-transfected cells (7%). Peptide sequence analysis revealed two potential nuclear localization signal (NLS) sequences in RGS3T. Further truncation of the RGS3T N terminus containing putative NLSs resulted in a significant reduction of nuclear versus cytoplasmic staining of the protein. Moreover, this truncated RGS3T no longer induced apoptosis. In summary, RGS3 and its truncated variant RGS3T are similar in their ability to inhibit G(q/11) signaling but are different in their intracellular distribution. These data suggest that, in addition to being a GTPase-activating protein, RGS3T has other distinct functions in the nucleus of the cell.

Animals↗

PubMed2006

A regulated nucleocytoplasmic shuttle contributes to Bright's function as a transcriptional activator of immunoglobulin genes.

Bright/ARID3a has been implicated in mitogen- and growth factor-induced up-regulation of immunoglobulin heavy-chain (IgH) genes and in E2F1-dependent G1/S cell cycle progression. For IgH transactivation, Bright binds to nuclear matrix association regions upstream of certain variable region promoters and flanking the IgH intronic enhancer. While Bright protein was previously shown to reside within the nuclear matrix, we show here that a significant amount of Bright resides in the cytoplasm of normal and transformed B cells. Leptomycin B, chromosome region maintenance 1 (CRM1) overexpression, and heterokaryon experiments indicate that Bright actively shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner. We mapped the functional nuclear localization signal to the N-terminal region of REKLES, a domain conserved within ARID3 paralogues. Residues within the C terminus of REKLES contain its nuclear export signal, whose regulation is primarily responsible for Bright shuttling. Growth factor depletion and cell synchronization experiments indicated that Bright shuttling during S phase of the cell cycle leads to an increase in its nuclear abundance. Finally, we show that shuttle-incompetent Bright point mutants, even if sequestered within the nucleus, are incapable of transactivating an IgH reporter gene. Therefore, regulation of Bright's cellular localization appears to be required for its function.

Active Transport, Cell Nucleus↗

PubMed2004

Nucleo-cytoplasmic shuttling of the beet necrotic yellow vein virus RNA-3-encoded p25 protein.

The protein p25 encoded by beet necrotic yellow vein virus (BNYVV) RNA-3 is involved in symptom expression of infected plants. Confocal microscopy analysis of wild-type and mutated p25 fused to GFP and transiently expressed in BY-2 tobacco suspension cells identified a nuclear localization signal (NLS) in the N-terminal part of the protein. Functionality of the NLS was confirmed by pull-down assays using rice and pepper importin-alpha. Furthermore, it was demonstrated that p25 contains a nuclear export sequence sensitive to leptomycin B. The nuclear export signal (NES) was characterized by mutagenesis. A GFP-p25 fusion protein expressed during a BNYVV infection of Chenopodium quinoa leaves had the same subcellular localization as observed during transient expression in BY-2 cells. The symptom phenotype induced by expression of GFP-p25 during infection was similar to that induced by wild-type virus. Studies with mutated derivatives of GFP-p25 revealed that symptom phenotype was altered when the subcellular localization of GFP-p25 was modified.

Active Transport, Cell Nucleus↗

PubMed2005

Specific inactivation and nuclear anchoring of extracellular signal-regulated kinase 2 by the inducible dual-specificity protein phosphatase DUSP5.

The mechanisms which determine the nuclear accumulation and inactivation of the extracellular signal-regulated kinase 1 (ERK1) or ERK2 mitogen-activated protein (MAP) kinases are poorly understood. Here we demonstrate that DUSP5, an inducible nuclear phosphatase, interacts specifically with ERK2 via a kinase interaction motif (KIM) within its amino-terminal noncatalytic domain. This binding determines the substrate specificity of DUSP5 in vivo, as it inactivates ERK2 but not Jun N-terminal protein kinase or p38 MAP kinase. Using green fluorescent protein fusions, we identify within this same domain of DUSP5 a functional nuclear localization signal (NLS) which functions independently of the KIM. Moreover, we demonstrate that the expression of DUSP5 causes both nuclear translocation and sequestration of inactive ERK2. Nuclear anchoring is ERK2 specific and requires both interactions between the DUSP5 KIM and the common docking site of ERK2 and a functional NLS within DUSP5. Finally, the expression of a catalytically inactive mutant of DUSP5 also tethers ERK2 within the nucleus. Furthermore, this nuclear ERK2 is phosphorylated by MAP kinase kinase in response to growth factors and also activates transcription factor Elk-1. We conclude that DUSP5 is an inducible nuclear ERK-specific MAP kinase phosphatase that functions as both an inactivator of and a nuclear anchor for ERK2 in mammalian cells. In addition, our data indicate that the cytoplasm may not be an exclusive site of MAP kinase activation.

Amino Acid Motifs↗

PubMed1996

Dynamic localization of the nuclear import receptor and its interactions with transport factors.

Characterization of the interactions between soluble factors required for nuclear transport is key to understanding the process of nuclear trafficking. Using a synthetic lethal screen with the rna1-1 strain, we have identified a genetic interaction between Rna1p, a GTPase activating protein required for nuclear transport, and yeast importin-beta, a component of the nuclear localization signal receptor. By the use of fusion proteins, we demonstrate that Rna1p physically interacts with importin-beta. Mutants in importin-beta exhibit in vivo nuclear protein import defects, and importin-beta localizes to the nuclear envelope along with other proteins associated with the nuclear pore complex. In addition, we present evidence that importin-alpha, but not importin-beta, mislocalizes to the nucleus in cells where the GTPase Ran is likely to be in the GDP-bound state. We suggest a model of nuclear transport in which Ran-mediated hydrolysis of GTP is necessary for the import of importin-alpha and the nuclear localization signal-bearing substrate into the nucleus, while exchange of GDP for GTP on Ran is required for the export of both mRNA and importin-alpha from the nucleus.

Amino Acid Sequence↗