Other entities represented in this entry:
HGNC Approved Gene Symbol: NUP98
Cytogenetic location: 11p15.4 Genomic coordinates (GRCh38): 11:3,675,010-3,797,554 (from NCBI)
In eukaryotic cells, the nucleus is spatially and functionally separated from the cytoplasm by the nuclear envelope. All molecular transport across the nuclear envelope takes place exclusively through the nuclear pore. Small molecules, such as ions and polypeptides smaller than approximately 40 kD, pass freely through the nuclear pore, but larger molecules require a carrier protein. The nuclear pore is formed by the nuclear pore complex (NPC), an 8-fold symmetrical structure composed of multiple copies of about 30 different proteins called nucleoporins. The NUP98 gene encodes a NUP98-NUP96 precursor protein that is cleaved by its own peptidase activity to produce 2 distinct nucleoporins, NUP98 and NUP96. Alternative splicing also generates NUP98 transcripts that encode NUP98, but not NUP96. NUP98 is a peripheral nucleoporin located at both the cytoplasmic and nuclear sides of the central channel of the NPC. It contains a characteristic gly-leu-phe-gly (GFLG) repeat region that contributes to nuclear-cytoplasmic trafficking, including mRNA export. NUP98 also plays roles in gene expression, mitotic checkpoint, and pathogenesis. NUP96 is a scaffold component of the NPC (review by Iwamoto et al., 2010).
Fontoura et al. (1999) identified NUP96 as a nucleoporin with a predicted molecular mass of 96 kD. NUP96 is generated through an unusual biogenesis pathway that involves synthesis of a 186-kD precursor protein. Proteolytic cleavage of the precursor yields 2 nucleoporins: NUP98 and NUP96. NUP96 is proteolytically cleaved in vivo. NUP96 is localized to the nucleoplasmic side of the NPC at or near the nucleoplasmic basket. The correct targeting of both NUP96 and NUP98 to the nucleoplasmic side of the NPC was found to be dependent on proteolytic cleavage, suggesting that the cleavage process may regulate NPC assembly.
In their review, Iwamoto et al. (2010) noted that alternative splicing produces 4 human NUP98 variants. Variants 1 and 4 are generated by alternative splicing in exon 20 and are translated into the NUP98-NUP96 precursor protein. Variants 2 and 3 are generated without splicing in exon 20 and are translated into NUP98 connected to a 57-amino acid polypeptide tail that is removed from NUP98 by autocleavage. Variants 1 and 4 differ from one another due to alternative splicing in exon 29, and variants 2 and 3 differ from one another due to alternative splicing in exon 10.
Nakamura et al. (1996) mapped the NUP98 gene to 11p15 by analysis of a panel of somatic cell hybrids and by pulsed field gel electrophoresis.
By immunogold electron microscopy, Radu et al. (1995) localized the NUP98 protein to the nucleoplasmic side of the nuclear pore. Nakamura et al. (1996) stated that ligand blot analysis suggested that NUP98 functions as a docking protein for cytosol-mediated docking of import substrates. The docking function has been localized to the N-terminal half of NUP98, the part of NUP98 that is retained in the NUP98/HOXA9 fusion (Radu et al., 1995).
Rosenblum and Blobel (1999) determined that no protease is involved in the processing of the NUP98-NUP96 precursor, but the molecule specifically cleaves itself between phe863 and ser864. The 2 fragments then form a low-affinity complex.
Von Kobbe et al. (2000) demonstrated that NUP98 is a target of the vesicular stomatitis virus M protein-mediated inhibition of mRNA nuclear export.
Enninga et al. (2002) demonstrated that NUP98 and NUP96 are upregulated by interferon. M protein-mediated inhibition of mRNA nuclear export was reversed when cells were treated with interferon-gamma (IFNG; 147570) or transfected with a cDNA encoding NUP98 and NUP96. Enninga et al. (2002) concluded that increased NUP98 and NUP96 expression constitutes an IFN-mediated mechanism that reverses M protein-mediated inhibition of gene expression.
Using a yeast 2-hybrid screen, Enninga et al. (2003) determined that SEC13L1 (600152) and an N-terminal region of NUP96 interact. By mutation analysis, they determined that the WD repeat region of SEC13L1 and residues 201 to 378 of NUP96 were required for the interaction. SEC13L1 did not bind NUP98. During mitosis, SEC13L1 was dispersed throughout the cell, whereas a pool of NUP96 colocalized with the spindle apparatus.
Jeganathan et al. (2005) showed that in mitosis, timely destruction of securin (604147) by the anaphase-promoting complex (APC) is regulated by the nucleocytoplasmic transport factors Rae1 (603343) and Nup98. They showed that combined haploinsufficiency for Rae1 and Nup98 in mice results in premature separation of sister chromatids, severe aneuploidy, and untimely degradation of securin. They also determined that Rae1 and Nup98 form a complex with cadherin-1 (Cdh1; 192090)-activated APC, APC(Cdh1), in early mitosis and specifically inhibit APC(Cdh1)-mediated ubiquitination of securin. Dissociation of Rae1 and Nup98 from APC(Cdh1) coincides with the release of the mitotic checkpoint protein BubR1 (602860) from Cdc20 (603618)-activated APC at the metaphase to anaphase transition. Jeganathan et al. (2005) concluded that together, their results suggest that Rae1 and Nup98 are temporal regulators of APC(Cdh1) that maintain euploidy by preventing unscheduled degradation of securin.
Zuccolo et al. (2007) stated that the NUP107 (607617)-NUP160 (607614) nucleoporin subcomplex contains NUP133 (607613), NUP96, NUP85 (170285), NUP43 (608141), NUP37 (609264), SEC13, and SEH1 (SEH1L; 609263). The NUP107-NUP160 subcomplex stably associates on both faces of NPCs during interphase, and the entire subcomplex is recruited to chromatin during mitosis. A fraction of the subcomplex localizes at kinetochores during prophase, even before nuclear envelope breakdown. Zuccolo et al. (2007) found that recruitment of the NUP107-NUP160 complex to kinetochores depended mainly on the NDC80 complex (see 607272) and CENPF (600236). The SEH1 subunit of the NUP107-NUP160 complex was essential for targeting the complex to kinetochores. Codepletion of several NUP107-NUP160 subunits or of SEH1 alone resulted in kinetochores that failed to establish proper microtubule attachment, thus inducing a checkpoint-dependent mitotic delay. The mitotic Ran-GTP effector, CRM1 (XPO1; 602559), as well as its binding partner, the RANGAP1 (602362)-RANBP2 (601181) complex, were mislocalized upon depletion of NUP107-NUP160 complex from kinetochores.
Wang et al. (2009) reported that fusing an histone H3 lysine-4 trimethylation (H3K4me3)-binding PHD finger, such as the C-terminal PHD finger of PHF23 (612910) or JARID1A (180202), to a common fusion partner NUP98, as identified in human leukemias (Reader et al., 2007; van Zutven et al., 2006), generated potent oncoproteins that arrested hematopoietic differentiation and induced acute myeloid leukemia in murine models. In these processes, a PHD finger that specifically recognizes H3K4me3/2 marks was essential for leukemogenesis. Mutations in PHD fingers that abrogated H3K4me3 binding also abolished leukemic transformation. NUP98-PHD fusion prevented the differentiation-associated removal of H3K4me3 at many loci encoding lineage-specific transcription factors such as Hox(s) (see 142950), Gata3 (131320), Meis1 (601739), Eya1 (601653), and Pbx1 (176310), and enforced their active gene transcription in murine hematopoietic stem/progenitor cells. Mechanistically, NUP98-PHD fusions act as 'chromatin boundary factors,' dominating over polycomb-mediated gene silencing to 'lock' developmentally critical loci into an active chromatin state (H3K4me3 with induced histone acetylation), a state that defined leukemia stem cells. Wang et al. (2009) concluded that their studies represented the first report that deregulation of the PHD finger, an effector of specific histone modification, perturbs the epigenetic dynamics on developmentally critical loci, leading to catastrophic cell fate decision making and oncogenesis during mammalian development.
Rapid disassembly of the NPC during mitotic entry requires the master mitotic kinase CDK1 (116940) and involves phosphorylation of many nucleoporins. Laurell et al. (2011) identified phosphorylation of NUP98 as an early and crucial step during NPC disassembly in HeLa cells. Recombinant NUP98 was hyperphosphorylated by PLK1 (602098), NEK6 (604884), and other NEK family members in vitro. Mass spectrometric analysis revealed that NUP98 was phosphorylated on ser591 and ser822 by NEK6 and on thr529, thr536, ser595, ser606, and thr653 by CDK1. Phosphomimetic mutants of NUP98 localized to the cytoplasm instead of NPCs. Conversely, phosphodeficient NUP98 mutants significantly delayed NPC disassembly and loss of the nuclear envelope permeability barrier. Laurell et al. (2011) concluded that NUP98 phosphorylation is critical for NPC disassembly at the onset of mitosis.
Hodel et al. (2002) reported that the 3-dimensional structure of the C-terminal domain of NUP98 revealed a novel protein fold, and thus a new class of autocatalytic proteases. The structure further indicated that the nucleoporin RNA-binding motif is unlikely to bind to RNA. The C terminus was found to contain sequences that target NUP98 to the nuclear pore complex. Noncovalent interactions between the C-terminal domain and the cleaved peptide tail were visible and suggested a model for cleavage-dependent targeting of NUP98 to the nuclear pore.
Lam and Aplan (2001) reviewed gene fusions involving NUP98. The NUP98 gene is fused to 1 of a considerable number of other genes in various hematologic malignancies as a consequence of chromosomal translocation. The common theme in all NUP98 chimeras is a transcript consisting of the 5-prime part of NUP98 and the 3-prime portion of the partner gene. However, apart from the frequent fusion to different homeobox genes, there is no apparent similarity among the other partners.
Nakamura et al. (1996) showed that in 3 patients with t(7;11), the chromosome rearrangement created a genomic fusion between the HOXA9 gene (142956) and the nucleoporin gene NUP98 on 11p15. Expression of Hoxa7 and Hoxa9 is activated by proviral integration in BXH2 murine myeloid leukemias; this result, combined with the mapping of the HOXA cluster to 7p15, suggested that one of the HOXA genes may be involved in the human t(7;11)(p15;p15) translocation found in some myeloid leukemia patients. The translocation produced an invariant chimeric NUP98/HOXA9 transcript containing the amino terminal half of NUP98 fused in-frame to HOXA9. These studies identified HOXA9 as an important human myeloid leukemia gene and suggested an important role for nucleoporins in human myeloid leukemia, given that a second nucleoporin, NUP214 (114350), had also been implicated in human myeloid leukemia. The 11p15 gene was identified by exon trapping experiments.
Borrow et al. (1996) likewise identified the HOXA9 and NUP98 genes as the parents of the fusion in t(7;11)(p15;p15) in acute myeloid leukemia of the FABM2 and M4 types. Borrow et al. (1996) suggested that the predicted NUP98/HOXA9 fusion protein may promote leukemogenesis through inhibition of HOXA9-mediated terminal differentiation and/or aberrant nucleocytoplasmic transport.
Hussey et al. (1999) identified the breakpoint genes of the translocation t(4;11)(q21;p15) that occurred in a case of adult T-cell acute lymphocytic leukemia (T-ALL). By analysis of somatic cell hybrids, they showed that the chromosome 11 breakpoint occurred within the NUP98 gene, which is rearranged in several acute myeloid leukemia translocations. Using 3-prime RACE, Hussey et al. (1999) identified the fusion partner of NUP98 as RAP1GDS1 (179502). This was the first report of the involvement of RAP1GDS1 in any malignancy. The product of the RAP1GDS1 gene, usually referred to as smgGDS, has guanine nucleotide exchange factor activity (Mizuno et al., 1991). In the fusion transcript, which the authors referred to as NRG, the 5-prime end of the NUP98 gene was joined in-frame to the coding region of the RAP1GDS1 gene. This joined the FG repeat-rich region of NUP98 to RAP1GDS1, which largely consists of tandem armadillo repeats. Hussey et al. (1999) found that the NRG fusion maintained the reading frame of RAP1GDS1. The RAP1GDS1 sequence in NRG started at nucleotide 5 of the coding sequence. The methionine and the first G of the codon for aspartic acid were lost. However, the first aspartic acid was retained in the fusion protein, because the last base of NUP98 exon B is a G. Hussey et al. (1999) showed that this translocation is recurrent in T-ALL.
Nakamura et al. (1999) studied a translocation fusion gene in acute myelogenous leukemia in which the promoter of the nucleoporin gene on 11p15 was fused to the DNA-binding domain of PRRX1 (167420).
Jaju et al. (1999) identified a recurrent cryptic translocation, t(5;11)(q35;p15.5), associated with a deletion of the long arm of chromosome 5 in de novo childhood acute myeloid leukemia (AML; see 601626). Jaju et al. (2001) confirmed that the chromosome 11 breakpoint gene is NUP98 and cloned the chromosome 5 fusion partner, NSD1 (606681). Nucleotide 1552 of NUP98 was fused in-frame to nucleotide 3504 of NSD1.
Constitutive activation of tyrosine kinases, such as the BCR/ABL (151410, 189980) fusion associated with t(9;22)(q34;q22), is a hallmark of chronic myeloid leukemia (CML; 608232) in humans. Expression of BCR/ABL is both necessary and sufficient to cause a chronic myeloproliferative syndrome in murine bone marrow transplantation models, and depends absolutely on kinase activity. Progression of CML to acute leukemia (blast crisis) in humans had been associated with acquisition of secondary chromosomal translocations, including the t(7;11)(p15;p15) resulting in the NUP98/HOXA9 fusion protein. Dash et al. (2002) demonstrated that BCR/ABL cooperates with NUP98/HOXA9 to cause blast crisis in the murine model. The phenotype depends on expression of both BCR/ABL and NUP98/HOXA9, but tumors retain sensitivity to the ABL inhibitor STI571 in vitro and in vivo. This paradigm is applicable to other constitutively activated tyrosine kinases such as TEL/PDGFRB (600618, 173410). The experiments of Dash et al. (2002) documented cooperative effects between constitutively activated tyrosine kinases, which confer proliferative and survival properties to hematopoietic cells, with mutations that impair differentiation, such as the NUP98/HOXA9 fusion, giving rise to the acute myeloid leukemia phenotype. Furthermore, these data indicated that despite acquisition of additional mutations, CML blast crisis cells retain their dependence on BCR/ABL for proliferation and survival.
Rosati et al. (2002) reported a fusion between the NUP98 and NSD3 (607083) genes in a patient with acute myeloid leukemia associated with t(8;11)(p11.2;p15). Hitherto, acute myeloid leukemia had been reported with translocations creating chimeric genes between NUP98 and PMX1 (PRRX1), HOXD13 (142989), NSD1, HOXA9, LEDGF, DDX10 (601235), and TOP1 (126420). In patients with T-cell acute lymphoblastic leukemia and t(4;11)(q21;p21), fusion of the NUP98 gene to the RAP1GDS1 gene had been observed (Hussey et al., 1999).
Arai et al. (1997) showed that the recurrent chromosome abnormality inv(11)(p15q22), which is associated with de novo and therapy-related myeloid malignancies, results in fusion of the nucleoporin gene NUP98 with DDX10. In DDX10 and NUP98, the inv(11) breakpoints occurred within 2 introns of each gene, and the 2 genes merged in-frame to produce the chimeric transcripts characteristic of this translocation. Although 2 reciprocal chimeric products, NUP98-DDX10 and DDX10-NUP98, were predicted, only NUP98-DDX10 appeared to be implicated in tumorigenesis. DDX10 is involved in ribosome assembly, and NUP98 is a nuclear pore complex protein and a target of other chromosomal translocations found in AML. Arai et al. (1997) predicted the NUP98-DDX10 fusion protein may promote leukemogenesis through aberrant nucleoplasmic transport of mRNA or alterations in ribosome assembly.
Ahuja et al. (1999) cloned and characterized a t(11;20)(p15;q11) translocation from patients with therapy-related AML and therapy-related myelodysplastic syndromes. They found that the breakpoint on 11p15 targets the NUP98 gene and results in the separation of the N-terminal FXFG repeats from the RNA-binding domain located in the C terminus. The breakpoint on 20q11 occurred within the TOP1 gene. As a result, a chimeric mRNA encoding the NUP98 FXFG repeats fused to the body of TOP1. Ahuja et al. (1999) concluded that NUP98 is a recurrent target in therapy-related malignancies and that TOP1 is a previously unrecognized target for chromosomal translocations.
Taketani et al. (2002) found that in the t(2;11)(q31;p15) translocation 2 alternatively spliced 5-prime NUP98 transcripts were fused in-frame to the HOXD11 gene (142986). The NUP98/HOXD fusion genes encode similar fusion proteins, suggesting that NUP98/HOXD11 and NUP98/HOXD13 fusion proteins play a role in leukemogenesis through similar mechanisms.
The NUP98 gene had been found at the breakpoints of several distinct chromosomal translocations in patients with both de novo and therapy-related myelodysplastic syndromes and AML. Using combined cytogenetic and molecular analyses, Ahuja et al. (2001) found rearrangements of the NUP98 gene in the leukemic cells of 2 patients with Philadelphia chromosome-positive CML during disease evolution. Analysis of the t(7;11)(p15;p15) translocation from 1 of the patients showed an in-frame NUP98/HOXA9 fusion. The fusion points were similar to those previously reported from patients with myelodysplastic syndromes or AML. The results indicated that the NUP98 gene is an additional, albeit infrequent, genetic target during clonal evolution of CML.
Panagopoulos et al. (2003) reported a patient with de novo AML with a t(11;12)(p15;q13) translocation resulting in a novel NUP98/HOXC13 (142976) fusion gene. FISH analyses showed a fusion signal on the derivative chromosome 11, indicating a NUP98/HOXC chimera, whereas no fusion was found on the derivative chromosome 12, suggesting that the reciprocal fusion gene was deleted. Thus, NUP98/HOXC13 is of pathogenetic importance in t(11;12)-positive AML.
Lahortiga et al. (2003) noted that the NUP98 gene had been reported to be fused to 13 partner genes in hematologic malignancies with 11p15 translocations. Twelve of the 13 had been identified in patients with myeloid neoplasias and only 1, RAP1GDS1, was fused with NUP98 in 5 patients with T-cell acute lymphoblastic leukemia. Three of these patients coexpressed T cell and myeloid markers, suggesting a specific association of RAP1GDS1 fusion with a subset of T-ALL originated from an early progenitor, which has a potential to express mature T-cell antigens as well as myeloid markers. Lahortiga et al. (2003) described a new NUP98 partner involved in a t(10;11)(q25;p15) in a patient with acute biphenotypic leukemia, showing coexpression of mature T cell and myeloid markers. The gene involved, located at 10q25, was identified as adducin-3 (ADD3; 601568) using 3-prime RACE. ADD3 codes for the ubiquitously expressed subunit gamma of the adducin protein and it seems to play an important role in the skeletal organization of the cell membrane. Both NUP98/ADD3 and ADD3/NUP98 fusion transcription were expressed in the patient. Adducin shares with the product of RAP1GDS1, and with all of the nonhomeobox NUP98 partners, the presence of a region with significant probability of adopting a coiled-coil conformation. This region is always retained in the fusion transcript with the NH2 terminus FG repeats of NUP98, suggesting an important role in the mechanism of leukemogenesis.
Ghannam et al. (2004) expressed a NUP98/HOXA9 fusion plasmid in human K562 myeloid leukemia cells. Microarray analysis revealed that the aberrant transcription factor had stronger and wider transcriptional effect than HOXA9 alone; NUP98 itself had no transcriptional activity. Ghannam et al. (2004) concluded that NUP98/HOXA9 requires the DNA-binding domain of HOXA9 for its activity.
Panagopoulos et al. (2007) reported the case of a fourth NUP98 chimera in T-cell acute lymphoblastic leukemia; a t(11;18)(p15;q12) resulted in a novel NUP98 fusion. They found that exon 12 of NUP98 was fused in-frame with exon 5 SETBP1. Nested PCR did not amplify the reciprocal SETBP1/NUP98, suggesting that the NUP98/SETBP1 transcript is pathogenetically important.
In a 42-year-old man with AML, Reader et al. (2007) identified a cryptic translocation, t(11;17)(p15;p13), that resulted in in-frame fusion of exon 13 of NUP98 to exon 4 of PHF23 (612910). The deduced chimeric protein contains the N-terminal half of NUP98 fused to the C-terminal functional domains of PHF23.
From a de novo acute T-lymphoid/myeloid leukemia harboring t(3;11)(q29q13;p15)del(3)(q29), Pan et al. (2008) identified a fusion between the NUP98 gene and the IQCG gene (612477). The fusion protein interacted with both NUP98 and IQCG, bound coactivators and/or corepressors, and showed transcriptional activity in vitro. However, by itself it did not appear to be sufficient to induce leukemia.
Such et al. (2011) identified a NUP98/RARG (180190) fusion gene resulting from a t(11;12)(p15;p13) translocation in bone marrow cells derived from a 35-year-old man with AML that had morphologic and immunophenotypic features of the hypergranular subtype of acute promyelocytic leukemia (APL; 612376). Sequence analysis determined that NUP98 exon 12 was fused in-frame to RARG exon 4, predicted to encode an 862-residue protein with aberrant RARG receptor function. The patient was treated with standard chemotherapy and bone marrow transplantation; response to ATRA was not assessed.
Tosi et al. (2005) identified a translocation, t(6;11)(q24.1;p15.5), in a patient with acute megakaryoblastic leukemia. RT-PCR and sequencing revealed a transcript that contained exon 13 of NUP98 fused in-frame with exon 2 of C6ORF80 (CCDC28A; 615353). The reciprocal fusion transcript was not detected.
Petit et al. (2012) found that the NUP98-CCDC28A transcript contains 1,833 nucleotides of NUP98 fused in-frame to nucleotide 384 of CDCD28A. The resultant 712-amino acid protein contains the N-terminal transactivating GLFG repeats of NUP98 fused to CCDC28A beginning at amino acid 77 and including its C-terminal coiled-coil domain. The fusion protein was expressed in the nucleus following transfection of primary mouse bone marrow cells. Immortalized mouse cells expressing human NUP98-CCDC28A exhibited myeloblast morphology, proliferated in a cytokine-independent manner, and caused fatal myeloproliferative neoplasms in transplanted mice, with selective expansion of granulocyte-macrophage progenitors in bone marrow.
Iwasaki et al. (2005) generated transgenic mice in which the NUP98/HOXA9 fusion gene was specifically expressed in the myeloid lineage under the control of the cathepsin G promoter. Approximately 20% of the transgenic mice developed acute myeloid leukemia after a long latency period. When NUP98/HOXA9 was introduced into the sensitive BXH2 mouse strain, it promoted onset of retrovirus-induced myeloid leukemia. By examining common retrovirus integration sites in these mice, Iwasaki et al. (2005) found that Meis1 (601739), Dnalc4 (610565), Fcgr2b (604590), Fcrl (606891), and Con1 cooperated with NUP98/HOXA9 in promoting the development of myeloid leukemias. Using a transformation assay with mouse NIH3T3 cells, Iwasaki et al. (2005) confirmed that these genes cooperated with NUP98/HOXA9 in inducing the transformed phenotype, although none alone were transforming.
Ahuja, H. G., Felix, C. A., Aplan, P. D. The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion. Blood 94: 3258-3261, 1999. [PubMed: 10556215]
Ahuja, H. G., Popplewell, L., Tcheurekdjian, L., Slovak, M. L. NUP98 gene rearrangements and the clonal evolution of chronic myelogenous leukemia. Genes Chromosomes Cancer 30: 410-415, 2001. [PubMed: 11241795] [Full Text: https://doi.org/10.1002/1098-2264(2001)9999:9999<::aid-gcc1108>3.0.co;2-9]
Arai, Y., Hosoda, F., Kobayashi, H., Arai, K., Hayashi, Y., Kamada, N., Kaneko, Y., Ohki, M. The inv(11)(p15q22) chromosome translocation of de novo and therapy-related myeloid malignancies results in fusion of the nucleoporin gene, NUP98, with the putative RNA helicase gene, DDX10. Blood 89: 3936-3944, 1997. [PubMed: 9166830]
Borrow, J., Shearman, A. M., Stanton, V. P., Jr., Becher, R., Collins, T., Williams, A. J., Dube, I., Katz, F., Kwong, Y. L., Morris, C., Ohyashiki, K., Toyama, K., Rowley, J., Housman, D. E. The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9. Nature Genet. 12: 159-167, 1996. [PubMed: 8563754] [Full Text: https://doi.org/10.1038/ng0296-159]
Dash, A. B., Williams, I. R., Kutok, J. L., Tomasson, M. H., Anastasiadou, E., Lindahl, K., Li, S., Van Etten, R. A., Borrow, J., Housman, D., Druker, B., Gilliland, D. G. A murine model of CML blast crisis induced by cooperation between BCR/ABL and NUP98/HOXA9. Proc. Nat. Acad. Sci. 99: 7622-7627, 2002. [PubMed: 12032333] [Full Text: https://doi.org/10.1073/pnas.102583199]
Enninga, J., Levay, A., Fontoura, B. M. A. Sec13 shuttles between the nucleus and the cytoplasm and stably interacts with Nup96 at the nuclear pore complex. Molec. Cell. Biol. 23: 7271-7284, 2003. [PubMed: 14517296] [Full Text: https://doi.org/10.1128/MCB.23.20.7271-7284.2003]
Enninga, J., Levy, D. E., Blobel, G., Fontoura, B. M. A. Role of nucleoporin induction in releasing an mRNA nuclear export block. Science 295: 1523-1525, 2002. [PubMed: 11809937] [Full Text: https://doi.org/10.1126/science.1067861]
Fontoura, B. M., Blobel, G., Matunis, M. J. A conserved biogenesis pathway for nucleoporins: proteolytic processing of a 186-kilodalton precursor generates Nup98 and the novel nucleoporin, Nup96. J. Cell Biol. 144: 1097-1112, 1999. [PubMed: 10087256] [Full Text: https://doi.org/10.1083/jcb.144.6.1097]
Ghannam, G., Takeda, A., Camarata, T., Moore, M. A., Viale, A., Yaseen, N. R. The oncogene Nup98-HOXA9 induces gene transcription in myeloid cells. J. Biol. Chem. 279: 866-875, 2004. [PubMed: 14561764] [Full Text: https://doi.org/10.1074/jbc.M307280200]
Hodel, A. E., Hodel, M. R., Griffis, E. R., Hennig, K. A., Ratner, G. A., Xu, S., Powers, M. A. The three-dimensional structure of the autoproteolytic, nuclear pore-targeting domain of the human nucleoporin Nup98. Molec. Cell 10: 347-358, 2002. [PubMed: 12191480] [Full Text: https://doi.org/10.1016/s1097-2765(02)00589-0]
Hussey, D. J., Nicola, M., Moore, S., Peters, G. B., Dobrovic, A. The (4;11)(q21;p15) translocation fuses the NUP98 and RAP1GDS1 genes and is recurrent in T-cell acute lymphocytic leukemia. Blood 94: 2072-2079, 1999. [PubMed: 10477737]
Iwamoto, M., Asakawa, H., Hiraoka, Y., Haraguchi, T. Nucleoporin Nup98: a gatekeeper in the eukaryotic kingdoms. Genes Cells 15: 661-669, 2010. [PubMed: 20545767] [Full Text: https://doi.org/10.1111/j.1365-2443.2010.01415.x]
Iwasaki, M., Kuwata, T., Yamazaki, Y., Jenkins, N. A., Copeland, N. G., Osato, M., Ito, Y., Kroon, E., Sauvageau, G., Nakamura, T. Identification of cooperative genes for NUP98-HOXA9 in myeloid leukemogenesis using a mouse model. Blood 105: 784-793, 2005. [PubMed: 15454493] [Full Text: https://doi.org/10.1182/blood-2004-04-1508]
Jaju, R. J., Fidler, C., Haas, O. A., Strickson, A. J., Watkins, F., Clark, K., Cross, N. C. P., Cheng, J.-F., Aplan, P. D., Kearney, L., Boultwood, J., Wainscoat, J. S. A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia. Blood 98: 1264-1267, 2001. [PubMed: 11493482] [Full Text: https://doi.org/10.1182/blood.v98.4.1264]
Jaju, R. J., Haas, O. A., Neat, M., Harbott, J., Saha, V., Boultwood, J., Brown, J. M., Pirc-Danoewinata, H., Krings, B. W., Muller, U., Morris, S. W., Wainscoat, J. S., Kearney, L. A new recurrent translocation, t(5;11)(q35p15.5), associated with del(5q) in childhood acute myeloid leukemia. Blood 94: 773-780, 1999. [PubMed: 10397745]
Jeganathan, K. B., Malureanu, L., van Deursen, J. M. The Rae1-Nup98 complex prevents aneuploidy by inhibiting securin degradation. Nature 438: 1036-1039, 2005. [PubMed: 16355229] [Full Text: https://doi.org/10.1038/nature04221]
Lahortiga, I., Vizmanos, J. L., Agirre, X., Vazquez, I., Cigudosa, J. C., Larrayoz, M. J., Sala, F., Gorosquieta, A., Perez-Equiza, K., Calasanz, M. J., Odero, M. D. NUP98 is fused to Adducin 3 in a patient with T-cell acute lymphoblastic leukemia and myeloid markers, with a new translocation t(10;11)(q25;p15). Cancer Res. 63: 3079-3083, 2003. [PubMed: 12810632]
Lam, D. H., Aplan, P. D. NUP98 gene fusions in hematologic malignancies. Leukemia 15: 1689-1695, 2001. [PubMed: 11681408] [Full Text: https://doi.org/10.1038/sj.leu.2402269]
Laurell, E., Beck, K., Krupina, K., Theerthagiri, G., Bodenmiller, B., Horvath, P., Aebersold, R., Antonin, W., Kutay, U. Phosphorylation of Nup98 by multiple kinases is crucial for NPC disassembly during mitotic entry. Cell 144: 539-550, 2011. [PubMed: 21335236] [Full Text: https://doi.org/10.1016/j.cell.2011.01.012]
Mizuno, T., Kaibuchi, K., Yamamoto, T., Kawamura, M., Sakoda, T., Fujioka, H., Matsuura, Y., Takai, Y. A stimulatory GDP/GTP exchange protein for smg p21 is active on the post-translationally processed form of c-Ki-ras p21 and rhoA p21. Proc. Nat. Acad. Sci. 88: 6442-6446, 1991. [PubMed: 1907371] [Full Text: https://doi.org/10.1073/pnas.88.15.6442]
Nakamura, T., Largaespada, D. A., Lee, M. P., Johnson, L. A., Ohyashiki, K., Toyama, K., Chen, S. J., Willman, C. L., Chen, I.-M., Feinberg, A. P., Jenkins, N. A., Copeland, N. G., Shaughnessy, J. D., Jr. Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia. Nature Genet. 12: 154-158, 1996. [PubMed: 8563753] [Full Text: https://doi.org/10.1038/ng0296-154]
Nakamura, T., Yamazaki, Y., Hatano, Y., Miura, I. NUP98 is fused to PMX1 homeobox gene in human acute myelogenous leukemia with chromosome translocation t(1;11)(q23;p15). Blood 94: 741-747, 1999. [PubMed: 10397741]
Pan, Q., Zhu, Y.-J., Gu, B.-W., Cai, X., Bai, X.-T., Yun, H.-Y., Zhu, J., Chen, B., Weng, L., Chen, Z., Xue, Y.-Q., Chen, S.-J. A new fusion gene NUP98-IQCG identified in an acute T-lymphoid/myeloid leukemia with a t(3;11)(q29q13;p15)del(3)(q29) translocation. Oncogene 27: 3414-3423, 2008. [PubMed: 18084320] [Full Text: https://doi.org/10.1038/sj.onc.1210999]
Panagopoulos, I., Isaksson, M., Billstrom, R., Strombeck, B., Mitelman, F., Johansson, B. Fusion of the NUP98 gene and the homeobox gene HOXC13 in acute myeloid leukemia with t(11;12)(p15;q13). Genes Chromosomes Cancer 36: 107-112, 2003. [PubMed: 12461755] [Full Text: https://doi.org/10.1002/gcc.10139]
Panagopoulos, I., Kerndrup, G., Carlsen, N., Strombeck, B., Isaksson, M., Johansson, B. Fusion of NUP98 and the SET binding protein 1 (SETBP1) gene in a paediatric acute T cell lymphoblastic leukaemia with t(11;18)(p15;q12). Brit. J. Haemat. 136: 294-296, 2007. [PubMed: 17233820] [Full Text: https://doi.org/10.1111/j.1365-2141.2006.06410.x]
Petit, A., Ragu, C., Soler, G., Ottolenghi, C., Schluth, C., Radford-Weiss, I., Schneider-Maunoury, S., Callebaut, I., Dastugue, N., Drabkin, H. A., Bernard, O. A., Romana, S., Penard-Lacronique, V. Functional analysis of the NUP98-CCDC28A fusion protein. Haematologica 97: 379-387, 2012. [PubMed: 22058212] [Full Text: https://doi.org/10.3324/haematol.2011.047969]
Radu, A., Moore, M. S., Blobel, G. The peptide repeat domain of nucleoporin Nup98 functions as a docking site in transport across the nuclear pore complex. Cell 81: 215-222, 1995. [PubMed: 7736573] [Full Text: https://doi.org/10.1016/0092-8674(95)90331-3]
Reader, J. C., Meekins, J. S., Gojo, I., Ning, Y. A novel NUP98-PHF23 fusion resulting from a cryptic translocation t(11;17)(p15;p13) in acute myeloid leukemia. (Letter) Leukemia 21: 842-844, 2007. [PubMed: 17287853] [Full Text: https://doi.org/10.1038/sj.leu.2404579]
Rosati, R., La Starza, R., Veronese, A., Aventin, A., Schwienbacher, C., Vallespi, T., Negrini, M., Martelli, M. F., Mecucci, C. NUP98 is fused to the NSD3 gene in acute myeloid leukemia associated with t(8;11)(p11.2;p15). Blood 99: 3857-3860, 2002. Note: Erratum: Blood 100: 1132 only, 2002. [PubMed: 11986249] [Full Text: https://doi.org/10.1182/blood.v99.10.3857]
Rosenblum, J. S., Blobel, G. Autoproteolysis in nucleoporin biogenesis. Proc. Nat. Acad. Sci. 96: 11370-11375, 1999. [PubMed: 10500183] [Full Text: https://doi.org/10.1073/pnas.96.20.11370]
Such, E., Cervera, J., Valencia, A., Barragan, E., Ibanez, M., Luna, I., Fuster, O., Perez-Sirvent, M. L., Senent, L., Sempere, A., Martinez, J., Martin-Aragones, G., Sanz, M. A. A novel NUPR98/RARG gene fusion in acute myeloid leukemia resembling acute promyelocytic leukemia. Blood 117: 242-245, 2011. [PubMed: 20935257] [Full Text: https://doi.org/10.1182/blood-2010-06-291658]
Taketani, T., Taki, T., Shibuya, N., Ito, E., Kitazawa, J., Terui, K., Hayashi, Y. The HOXD11 gene is fused to the NUP98 gene in acute myeloid leukemia with t(2;11)(q31;p15). Cancer Res. 62: 33-37, 2002. [PubMed: 11782354]
Tosi, S., Ballabio, E., Teigler-Schlegel, A., Boultwood, J., Bruch, J., Harbott, J. Characterization of 6q abnormalities in childhood acute myeloid leukemia and identification of a novel t(6:11)(q24.1;p15.5) resulting in a NUP98-C6orf80 fusion in a case of acute megakaryoblastic leukemia. Genes Chromosomes Cancer 44: 225-232, 2005. [PubMed: 16028218] [Full Text: https://doi.org/10.1002/gcc.20233]
van Zutven, L. J. C. M., Onen, E., Velthuizen, S. C. J. M., van Drunen, E., von Bergh, A. R. M., van den Heuvel-Eibrink, M. M., Veronese, A., Mecucci, C., Negrini M., de Greef, G. E., Berna Beverloo, H. Identification of NUP98 abnormalities in acute leukemia: JARID1A (12p13) as a new partner gene. Genes Chromosomes Cancer 45: 437-446, 2006. [PubMed: 16419055] [Full Text: https://doi.org/10.1002/gcc.20308]
von Kobbe, C., van Deursen, J. M. A., Rodrigues, J. P., Sitterlin, D., Bachi, A., Wu, X., Wilm, M., Carmo-Fonseca, M., Izaurralde, E. Vesicular stomatitis virus matrix protein inhibits host cell gene expression by targeting the nucleoporin Nup98. Molec. Cell 6: 1243-1252, 2000. [PubMed: 11106761] [Full Text: https://doi.org/10.1016/s1097-2765(00)00120-9]
Wang, G. G., Song, J., Wang, Z., Dormann, H. L., Casadio, F., Li, H., Luo, J.-L., Patel, D. J., Allis, C. D. Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger. Nature 459: 847-851, 2009. [PubMed: 19430464] [Full Text: https://doi.org/10.1038/nature08036]
Zuccolo, M., Alves, A., Galy, V., Bolhy, S., Formstecher, E., Racine, V., Sibarita, J.-B., Fukagawa, T., Shiekhattar, R., Yen, T., Doye, V. The human Nup107-160 nuclear pore subcomplex contributes to proper kinetochore functions. EMBO J. 26: 1853-1864, 2007. [PubMed: 17363900] [Full Text: https://doi.org/10.1038/sj.emboj.7601642]