Copy number loss in the region of the ASPN gene in patients with acetabular dysplasia: ASPN CNV in acetabular dysplasia.

OBJECTIVES: We have previously investigated an association between the genome copy number variation (CNV) and acetabular dysplasia (AD). Hip osteoarthritis is associated with a genetic polymorphism in the aspartic acid repeat in the N-terminal region of the asporin (ASPN) gene; therefore, the present study aimed to investigate whether the CNV of ASPN is involved in the pathogenesis of AD. METHODS: Acetabular coverage of all subjects was evaluated using radiological findings (Sharp angle, centre-edge (CE) angle, acetabular roof obliquity (ARO) angle, and minimum joint space width). Genomic DNA was extracted from peripheral blood leukocytes. Agilent's region-targeted high-density oligonucleotide tiling microarray was used to analyse 64 female AD patients and 32 female control subjects. All statistical analyses were performed using EZR software (Fisher's exact probability test, Pearson's correlation test, and Student's t-test). RESULTS: CNV analysis of the ASPN gene revealed a copy number loss in significantly more AD patients (9/64) than control subjects (0/32; p = 0.0212). This loss occurred within a 60 kb region on 9q22.31, which harbours the gene for ASPN. The mean radiological parameters of these AD patients were significantly worse than those of the other subjects (Sharp angle, p = 0.0056; CE angle, p = 0.0076; ARO angle, p = 0.0065), and all nine patients required operative therapy such as total hip arthroplasty or pelvic osteotomy. Moreover, six of these nine patients had a history of operative or conservative therapy for developmental dysplasia of the hip. CONCLUSIONS: Copy number loss within the region harbouring the ASPN gene on 9q22.31 is associated with severe AD. A copy number loss in the ASPN gene region may play a role in the aetiology of severe AD.Cite this article: T. Sekimoto, M. Ishii, M. Emi, S. Kurogi, T. Funamoto, Y. Yonezawa, T. Tajima, T. Sakamoto, H. Hamada, E. Chosa. Copy number loss in the region of the ASPN gene in patients with acetabular dysplasia: ASPN CNV in acetabular dysplasia. Bone Joint Res 2017;6:439-445. DOI: 10.1302/2046-3758.67.BJR-2016-0094.R1.

Possible association of single nucleotide polymorphisms in the 3' untranslated region of HOXB9 with acetabular overcoverage.

OBJECTIVES: Excessive acetabular coverage is the most common cause of pincer-type femoroacetabular impingement. To date, an association between acetabular over-coverage and genetic variations has not been studied. In this study we investigated the association between single nucleotide polymorphisms (SNPs) of paralogous Homeobox (HOX)9 genes and acetabular coverage in Japanese individuals to identify a possible genetic variation associated with acetabular over-coverage. METHODS: We investigated 19 total SNPs in the four HOX9 paralogs, then focused in detail on seven of those located in the 3' untranslated region of HOXB9 (rs8844, rs3826541, rs3826540, rs7405887, rs2303485, rs2303486, rs79931349) using a case-control association study. The seven HOXB9 SNPs were genotyped in 316 subjects who had all undergone radiological examination. The association study was performed by both single-locus and haplotype-based analyses. RESULTS: The genotype and allele frequencies of the five HOXB9 SNPs showed significant association with acetabular over-coverage compared with controls (rs7405887 OR = 3.16, p = 5.29E-6, 95% CI 1.91 to 5.25). A significant difference was also detected when haplotypes were evaluated (OR = 2.59, p = 2.61E-5, 95% CI 1.65 to 4.08). The two HOXB9 SNPs (rs2303485, rs2303486) were associated with decreased acetabular coverage (rs2303485 OR = 0.524, p = 0.0091, 95% CI 0.322 to 0.855; rs2303486 OR = 0.519, p = 0.011, 95% CI 0.312 to 0.865). CONCLUSIONS: The five HOXB9 SNPs (rs8844, rs3826541, rs3826540, rs7405887, rs79931349) were associated with acetabular over-coverage. On the other hand, the two SNPs (rs2303485 and rs2303486) were associated with the lower acetabular coverage. The association of rs2303486 would be consistent with the previous study. Therefore, the HOXB9 SNPs might be involved in the morphogenesis of acetabular coverage, and could be an independent risk factor for developing pincer-type femoroacetabular impingement. Cite this article: Bone Joint Res 2015;4:50-5.

Sonographic and clinical features of collateral vessels at the splenic hilum in cirrhosis.

AIM: To examine the sonographic features of shunt vessels derived from the splenic vein at splenic hilum (SS), and explore the relationship between the SS pattern and clinical presentations. MATERIALS AND METHODS: This prospective study in cirrhotic patients consisted of study I (n = 15), which compared the anatomical features of SS at ultrasonography versus angiography, and study II (n = 233), which examined the incidence/haemodynamics of SS and SS-related presentations. RESULTS: Study I showed that SS1 (running toward the upper pole of the spleen) corresponded to short gastric veins, and SS2 (running toward the lower pole of the spleen) corresponded to splenorenal/retroperitoneal shunts. In study II, SS were detected in 47.6% of patients (111/233), SS1 in 77.5% (86/111), SS2 in 17.1% (19/111), and SS3 (both SS1 and SS2) in 5.4% (6/111). The incidence of gastric cardia varices was significantly higher in patients with SS2 (6/19) than in those with SS1 (8/86, p = 0.0097), whereas the incidence of gastric fundal varices was significantly higher in patients with SS1 (44/86) than in those with SS2 (1/19, p = 0.00025) or SS3 (0/6, p = 0.015). There was no difference in the incidence of oesophageal varices among the three SS groups. The Child-Pugh score and grade of ascites was significantly worse in patients with SS3 than in those with SS1 (p < 0.0001, p = 0.0009). Hepatic encephalopathy grade was significantly worse in patients with SS2 (p = 0.0047) or SS3 (p < 0.0001) compared to SS1. CONCLUSION: The SS pattern facilitates estimation of the possible manifestations, indicating the direction of clinical management of cirrhosis patients. Potential poor liver function is noted in patients with SS3.

20-Hydroxyecdysone regulation of two isoforms of the Ets transcription factor E74 gene in programmed cell death in the silkworm anterior silk gland.

Programmed cell death of larval-specific tissues in insects is under the control of 20-hydroxyecdysone (20E). The ecdysteroid-regulated early genes are conserved in the programmed cell death of anterior silk glands (ASGs) in Bombyx mori and salivary glands in Drosophila melanogaster. We identified and characterized two isoforms of the Ets transcription factor E74 gene in B. mori (BmE74). In ASGs of B. mori last instar larvae, the Bm74A mRNA level increased concomitantly with an increase in haemolymph ecdysteroid titre after gut purge. The optimal 20E concentration for stimulation of Bm74A in ASGs was 4 microM, a similar value to the peak haemolymph ecdysteroid concentration after gut purge. In contrast, BmE74B expression peaked on day 5 of the feeding period, after which it did not increase again. These findings suggest that the BmE74 isoforms play different roles in the regulation of programmed cell death in B. mori ASGs.

Coordinate responses of transcription factors to ecdysone during programmed cell death in the anterior silk gland of the silkworm, Bombyx mori.

Programmed cell death (PCD) in Bombyx mori anterior silk glands (ASGs) is triggered by 20-hydroxyecdysone (20E). We examined the expression profiles and effects of 20E on 11 transcription factor genes in the fifth instar to determine whether they demonstrate the hierarchical control seen in Drosophila PCD. Results indicate that EcR-A and usp-2, but not EcR-B1 or usp-1, may be components of the ecdysone receptor complex. Up-regulation of E75A, BHR3, and three BR-C isoforms, but not E75B, appeared to be associated with the induction of PCD. betaFTZ-F1 was not expressed during PCD execution. Thus, gene control in B. mori ASGs differs from that in Drosophila salivary glands, despite both tissues undergoing PCD in response to 20E at pupal metamorphosis.

Identification of a novel allele HLA-A*1113 in a Japanese donor.

Anew HLA-A*11 allele, A*1113, was identified in a healthy Japanese female. She was typed as HLA-A11?, A2, B46, B67, Cw1, Cw7 (Bw6) with unusual serological reactivity of A11, suggesting possible presence of a new A*11 allele. The novel A*1113 allele was identified by haplotypic group-specific allele amplification using A*11 allele-specific primer pairs and sequence-based typing. The A*1113 allele differs from A*11011 by one nucleotide substitution in exon 3 at position 503 (A --> G) which causes an amino acid change in the alfa2 domain at residue 144 (lysine : K --> arginine : R), thus resulting in the unusual serological reactivity.

The YXXQ motif in gp 130 is crucial for STAT3 phosphorylation at Ser727 through an H7-sensitive kinase pathway.

The signal transducer and activator of transcription (STAT) 3 is essential for mediating signals from the receptors for a variety of cytokines and growth factors, including IL-6 and EGF, and from cytoplasmic tyrosine kinases. Upon stimulation, STAT3 is phosphorylated at Ser727 and Tyr705. However, the role of phosphorylation at Ser727, and the kinase pathways responsible for this phosphorylation in IL-6 signaling remain obscure. Here we show that IL-6 activates at least two distinct STAT3 serine kinase pathways and that an H7-sensitive pathway is dominant over a PD98059-sensitive one in HepG2 cells stimulated with a low concentration of IL-6. The analysis, using a series of chimeric receptors containing the extracellular domain of the G-CSF receptor, the truncated form of gp 130, and additional short peptides at the gp 130 carboxy-terminus, showed that the YXXQ motif of gp 130 was sufficient for the H7-sensitive STAT3 Ser727 phosphorylation. This YXXQ-mediated pathway does not involve Erk, p38, JNK, or PKCdelta, and requires a site in the region from 533 to 711 of STAT3 for phosphorylation in vivo. Moreover, we show that Ser727 is required for full transcriptional activity of STAT3 for two different response elements. Thus, the YXXQ motif regulates STAT3 activities in two ways in response to even a low concentration of IL-6: it recruits STAT3 to the receptor for tyrosine phosphorylation, and activates an unidentified H7-sensitive pathway leading to the serine phosphorylation of STAT3.

Neonatal alloimmune thrombocytopenia due to anti-human leukocyte antigen antibody: a case report.

Anti-HLA antibodies reportedly exist in 31% of pregnant women. However, few ocurrences of neonatal alloimmune thrombocytopenia (NAIT) caused by anti-HLA antibody have been reported. In this study, maternal anti-HLA B60 and B61 antibodies were identified in patient serum at birth, but no anti-platelet antibodies were present. No maternal anti-HLA A2, A24, B51, or B52 antibodies were detected in patient serum. Platelet transfusion from the third donor was effective because these platelets expressed HLA A24 and B52 but not B60 or B61. Cross-matching tests between patient leukocytes or platelets and maternal serum were strongly positive, indicating that maternal anti-HLA antibodies were responsible for NAIT. This report is the first to demonstrate NAIT probably caused by maternal anti-HLA A24 and B52.

Identification of a novel allele HLA-B*7805 in a Japanese female.

A new HLA-B*78 allele, B*7805, was identified in a healthy Japanese female. The results of her serological HLA class I typing showed an unusual Bw4/Bw6 pattern with strongly positive reactivity to anti-Bw6, i.e. A24, -, B52, -, Bw4, Bw6. In DNA typing, she was typed as A*24, -, B*52, B*78-like, Cw1202, -, (Bw4, Bw6). Cloning and sequencing of exon 2 and exon 3 of her B locus genes revealed a new allele B*7805. The cloned B*7805 differed from B*78021 by three nucleotide substitutions in exon 2 at position 259 (A to G), 261 (C to G) and 272 (A to C), and contained sequences defining Bw6 motif in the region of codon 77 to 83.

Vertical antiresonant reflecting optical waveguide coupler for three-dimensional optical interconnects: optimum design for large tolerance, high coupling efficiency, and short coupling length.

A compact antiresonant-reflecting-optical-waveguide-(ARROW-) type vertical coupler for three-dimensional optical interconnects was demonstrated. The coupler consists of stacked ARROW's channeled by the stripe lateral confinement structure, and each waveguide is completely separated by a thin metal film in the separation region. In the coupling region the intermediate cladding of a previous coupler was made of the same material as that of the first cladding or the core. However, we had to overcome the problem that both the high coupling efficiency and the large fabrication tolerance cannot be achieved simultaneously. Thus we incorporated an intermediate cladding made of a material different from that of the core and the first cladding. The refractive index and the thickness of the intermediate cladding were optimally designed to achieve large fabrication tolerance and a short coupling length with a high coupling efficiency. The coupling length was reduced from 4.1 to 0.8 mm, and a high coupling efficiency of 96% was experimentally demonstrated.

Evaluation of phosphoinositide turnover on ischemic human brain with 1-[1-11C]-butyryl-2-palmitoyl-rac-glycerol using PET.

UNLABELLED: It is important to evaluate cerebral function from neural signal transduction in ischemic brain in judging morbid state and prognosis. We synthesized 1-[1-(11)C]-butyryl-2-palmitoyl-rac-glycerol (DAG) for the purpose of imaging the second messenger on PET and applied it to clinical cases of cerebral infarction. METHODS: Five patients, who had ischemic stroke, were examined with PET. [15O]-CO2 and [15O]-O2 inhalation methods were applied to cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2). For the measurement of phosphoinositide turnover after intravenous injection of DAG, dynamic PET data were collected continuously for 46 min. Arterial blood samples were taken to evaluate changes in the serum concentration of DAG. To quantify the metabolic activity of inositol phospholipid, the incorporation constant k*(DAG) was calculated on the basis of the kinetics of DAG. RESULTS: The plasma concentration of DAG increased rapidly and peaked 30 s after injection of DAG solution. In the normal cortex, DAG concentration increased gradually and reached a plateau between 15 and 20 min after injection. In the ischemic core (infarction), DAG concentration increased slowly, and its peak concentration was lower than that in normal tissue. In comparison with blood flow and metabolic parameters, k*(DAG) showed the best correlation with CMRO2, suggesting a reflection of neuronal activity. Locally, CBF and CMRO2 gradually decreased from the normal area toward the ischemic center (infarction), whereas k*(DAG) and OEF significantly decreased only in the ischemic center. CONCLUSION: The k*(DAG) of ischemic brain, including that caused by infarction, significantly correlated with CMRO2, suggesting that metabolic activity of inositol phospholipid reflects neural viability. Maintained metabolic activity of inositol phospholipid in the region around the ischemic core indicated preservation of the signal transduction system through the metabotropic receptor.

Exchangeable gene trap using the Cre/mutated lox system.

The gene trap technique is a powerful approach for characterizing and mutating genes involved in mouse development. However, one shortcoming of gene trapping is the relative inability to induce subtle mutations. This problem can be overcome by introducing a knock-in system into the gene trap strategy. Here, we have constructed a new gene trap vector, pU-Hachi, employing the Cre-mutated lox system (Araki et al., 1997), in which a pair of mutant lox, lox71 and lox66, was used to promote targeted integrative reaction by Cre recombinase. The pU-Hachi carries splicing acceptor (SA)-lox71-internal ribosomal entry site (IRES)-beta-geo-pA-loxP-pA-pUC. By using this vector, we can carry out random insertional mutagenesis as the first step, and then we can replace the beta-geo gene with any gene of interest through Cre-mediated integration. We have isolated 109 trap clones electroporated with pU-Hachi, and analyzed their integration patterns by Southern blotting to select those carrying a single copy of the trap vector. By use of some of these clones, we have succeeded in exchanging the reporter gene at high efficiency, ranging between 20-80%. This integration system is also quite useful for plasmid rescue to recover flanking genomic sequences, because a plasmid vector sequence can be introduced even when the pUC sequence of the trap vector is lost through integration into the genome. Thus, this method, termed exchangeable gene trapping, has many advantages as the trapped clones can be utilized to express genes with any type of mutation.

Effect of cutting instruments on permeability and morphology of the dentin surface.

There are major differences in morphological detail after cutting the dentin surface among the methods commonly used to prepare dental cavities. The purpose of this study was to compare dentin permeability and the morphology of the dentin surfaces prepared with diamond and carbide steel burs after etching with 6% citric acid. Twenty-four freshly extracted human third molars were sectioned, mounted on plexiglass, and connected to the dentin-permeability measuring apparatus. The permeability of dentin was measured by fluid filtration and expressed as hydraulic conductance. There were two study groups of 12 teeth. Each tooth had one occlusal cavity preparation prepared but utilized three depths: the original was prepared just into the dentin, the second 0.5 mm deeper than the first, and the third 0.5 mm deeper than the second. One group had the first cavity prepared with a diamond, the second deepened using a steel bur, then the third depth was made by use of the diamond. The other group had the first cavity preparation prepared with a steel bur, deepened 0.5 mm again using a diamond, then deepened again using a steel bur. Dentin permeability was measured after cavity preparation, then after 2 minutes of acid etching. Analysis of variance and Duncan's multiple range test were used to establish whether differences were significant at the 0.05 confidence level. Prepared and acid-etched surfaces were characterized using a scanning electron microscope to identify any differences between the two groups. After acid etching with 6% citric acid, the permeability of dentin cavities prepared with diamond burs was significantly less than the permeability of cavities prepared with carbide steel burs. After etching, there were differences in the appearance of the dentin surfaces prepared with diamonds and steel burs. Dentin bonding agents may have their effectiveness reduced when placed following cavity preparation by use of a diamond.

Leptomycin B inhibition of signal-mediated nuclear export by direct binding to CRM1.

Leptomycin B (LMB) is a Streptomyces metabolite that inhibits nuclear export of the human immunodeficiency virus type 1 regulatory protein Rev at low nanomolar concentrations. Recently, LMB was shown to inhibit the function of CRM1, a receptor for the nuclear export signal (NES). Here we show evidence that LMB binds directly to CRM1 and that CRM1 is essential for NES-dependent nuclear export of proteins in both yeast and mammalian cells. Binding experiments with a biotinylated derivative of LMB and a HeLa cell extract led to identifying CRM1 as a major protein that bound to the LMB derivative. Microinjection of a purified anti-human CRM1 antibody into the mammalian nucleus specifically inhibited nuclear export of NES-containing proteins, as did LMB. Consistent with this, CRM1 was found to interact with NES, when assayed with immobilized NES and HeLa cell extracts. This association was disrupted by adding LMB or purified anti-human CRM1 antibody. The inhibition of CRM1 by LMB was also observed in fission yeast. The fission yeast crm1 mutant was defective in the nuclear export of NES-fused proteins, but not in the import of nuclear localization signal (NLS)-fused proteins. Interestingly, a protein containing both NES and NLS, which is expected to shuttle between nucleus and cytoplasm, was highly accumulated in the nucleus of the crm1 mutant cells or of cells treated with LMB. These results strongly suggest that CRM1 is the target of LMB and is an essential factor for nuclear export of proteins in eukaryotes.

Region-specific expression of murine Hox genes implies the Hox code-mediated patterning of the digestive tract.

BACKGROUND: Hox genes encode transcription factors which are involved in the establishment of regional identities along the anteroposterior (AP) body axis. To elucidate the AP patterning of the digestive tract, we have systematically examined the expression patterns of Hox genes belonging to paralogue groups 6, 7, 8 and 9 by whole-mount in situ hybridization and by section in situ hybridization analyses. RESULTS: The expression patterns of these genes showed co-linearity along the wall of the digestive tract, thereby yielding the Hox code of the gut. The expression boundaries of the Hox genes at later stages (12.5 d.p.c.) corresponded to the morphological boundaries of individual gut subdomains. CONCLUSIONS: The visceral mesoderm-restricted expression suggested that the Hox code primarily functions in the mesenchymal specification which eventually leads to the regional differentiation of gut subdomains as the result of epithelial-mesenchymal interactions. Overlapping expression patterns were found among the paralogous Hox genes, indicating that the paralogues may have redundant functions in the specification of the gut.

Nuclear import and export of proteins: the molecular basis for intracellular signaling.

A family of latent cytoplasmic transcription factors termed Stats are activated by a variety of cytokines, and are then translocated into the nucleus where they activate transcription. Recent advances in nuclear protein import have shown that the extracellular signal-dependent nuclear import of Stat1 is mediated via complex formation with NPI-1 (a member of the alpha subunit family) and the beta subunit of the nuclear pore-targeting complex, and a small GTPase, Ran. The unique transport pathway of Stat1, which is different from that of the SV40T-antigen, indicates that a complex divergence exists in the function of transport factors and transport pathways.

Differential modes of nuclear localization signal (NLS) recognition by three distinct classes of NLS receptors.

The targeting of karyophilic proteins to nuclear pores is mediated via the formation of a nuclear pore-targeting complex, through the interaction of nuclear localization signal (NLS) with its NLS receptor. Recently, a novel human protein, Qip1, was identified from a yeast two-hybrid system with DNA helicase Q1. This study demonstrates that Qip1 is a novel third class of NLS receptor that efficiently recognizes the NLS of the helicase Q1. Moreover, the data obtained in this study show that the specific interaction between Qip1 and the NLS of the helicase Q1 requires its upstream sequence of the minimal essential NLS. By using purified recombinant proteins alone in the digitonin-permeabilized cell-free transport system, it was demonstrated that the two known human NLS receptors, Rch1 and NPI-1, are able to transport all the tested NLS substrates into the nucleus, while Qip1 most efficiently transports the helicase Q1-NLS substrates, which contain its upstream sequence in so far as we have examined the system. Furthermore, in HeLa cell crude cytosol, it was found that endogenous Rch1 binds to all the tested NLS substrates, while the binding of endogenous NPI-1 is restricted to only some NLSs, despite the fact that NPI-1 itself shows binding activity to a variety of NLSs. These results indicate that at least three structurally and functionally distinct NLS receptors exist in the human single cell population, and suggest that the nuclear import of karyophilic proteins may be controlled in a complex manner at the NLS recognition step by the existence of a variety of NLS receptors with various specificities to each NLS.

Extracellular signal-dependent nuclear import of Stat1 is mediated by nuclear pore-targeting complex formation with NPI-1, but not Rch1.

In response to interferon-gamma (IFN-gamma), Stat1 is tyrosine phosphorylated and translocates to the nucleus where it activates transcription. In this study, we identified factors which mediate the nuclear import of Stat1. Tyrosine-phosphorylated Stat1 associated with the beta subunit (a 97 kDa component) of the nuclear pore-targeting complex via the NPI-1 family, but not the Rch1 family, of alpha subunit (a 58 kDa component) as a result of IFN-gamma stimulation. Antibodies against NPI-1 or beta subunit consistently inhibited the IFN-gamma-dependent nuclear import of Stat1 in living cells, although antibodies reactive to Rch1 had no effect. Solution binding assays with deletion mutants of NPI-1 showed that the Stat1-binding domain of NPI-1 was located in the carboxy-terminal region, which is clearly distinct from the SV40 large T antigen nuclear localization signal (NLS)-binding region. These results indicate that the extracellular signal-dependent nuclear transport of Stat1 is mediated by NPI-1, but not Rch1, in conjunction with beta subunit, and that these factors participate in, not only constitutive, but also the conditional nuclear import of proteins.

Interferon-gamma-dependent nuclear import of Stat1 is mediated by the GTPase activity of Ran/TC4.

In response to interferon-gamma (IFN-gamma), Stat1 enters the nucleus, where it activates transcription. In order to better understand the mechanism of the extracellular signal-induced protein import into the nucleus, we have established an in vivo assay system that uses recombinant Stat1 protein as a model transport substrate. Using this system, we found that Stat1 is actively transported through the nuclear pores in an IFN-gamma-dependent manner and tyrosine (Tyr701) phosphorylation of Stat1 is actually required for its nuclear import. When the antibody against Ran, which was identified as an essential factor for active nuclear protein transport, was injected, the IFN-gamma-dependent nuclear transport of Stat1 was completely inhibited. Furthermore, nuclear import of Stat1 was suppressed by microinjection of two mutant Ran proteins, one defective in GTP hydrolysis (G19V) and the other with little or no binding to GTP (T24N), both of which are known to act as dominant negative inhibitors of nuclear import. These results indicate that the conditional nuclear import of Stat1 requires GTP hydrolysis by Ran.

Exogenously injected nuclear import factor p10/NTF2 inhibits signal-mediated nuclear import and export of proteins in living cells.

p10/NTF2 is a cytosolic factor which is required for the translocation step in nuclear protein import in an in vitro assay with digitonin-permeabilized cells. To study the functional roles of p10/NTF2 on protein transport between the nucleus and cytoplasm in living cells, recombinant p10/NTF2 was micro-injected into cultured mammalian cells. Cytoplasmically injected p10/NTF2 strongly inhibited the nuclear import of co-injected NLS-containing substrates in a dose-dependent manner but had no effect on the diffusive import of small non-nuclear proteins. Moreover, when injected into the cell nucleus, p10/NTF2 inhibited the nuclear export of NES-containing substrates. The results suggest that the nuclear import factor p10/NTF2 may also be involved in the nuclear export of proteins and that the protein transport efficiency between the nucleus and cytoplasm may be regulated by the intracellular level of p10/NTF2.