alpha karyopherins


Summary: Nucleocytoplasmic transport molecules that bind to the NUCLEAR LOCALIZATION SIGNALS of cytoplasmic molecules destined to be imported into the CELL NUCLEUS. Once attached to their cargo they bind to BETA KARYOPHERINS and are transported through the NUCLEAR PORE COMPLEX. Inside the CELL NUCLEUS alpha karyopherins dissociate from beta karypherins and their cargo. They then form a complex with CELLULAR APOPTOSIS SUSCEPTIBILITY PROTEIN and RAN GTP-BINDING PROTEIN which is exported to the CYTOPLASM.

Top Publications

  1. Freedman N, Yamamoto K. Importin 7 and importin alpha/importin beta are nuclear import receptors for the glucocorticoid receptor. Mol Biol Cell. 2004;15:2276-86 pubmed
    ..Interestingly, importin 7, importin 8, and importin alpha bound GR even in the absence of hormone; thus, hormonal control of localization is exerted at a step downstream of import receptor binding. ..
  2. Maertens G, Cherepanov P, Debyser Z, Engelborghs Y, Engelman A. Identification and characterization of a functional nuclear localization signal in the HIV-1 integrase interactor LEDGF/p75. J Biol Chem. 2004;279:33421-9 pubmed
    ..Moreover, a single amino acid change in the NLS was sufficient to exclude the mutant LEDGF/p75 protein from the nucleus and abolish nuclear import of HIV-1 integrase. ..
  3. Kotera I, Sekimoto T, Miyamoto Y, Saiwaki T, Nagoshi E, Sakagami H, et al. Importin alpha transports CaMKIV to the nucleus without utilizing importin beta. EMBO J. 2005;24:942-51 pubmed
    ..This is the first report to demonstrate definitely that mammalian importin alpha solely carries a cargo protein into the nucleus without utilizing the classical importin beta-dependent transport system. ..
  4. Hodel A, Harreman M, Pulliam K, Harben M, Holmes J, Hodel M, et al. Nuclear localization signal receptor affinity correlates with in vivo localization in Saccharomyces cerevisiae. J Biol Chem. 2006;281:23545-56 pubmed
    ..This correlation, however, is not maintained for cargoes that bind to the NLS receptor with very weak or very strong affinity. ..
  5. Reid S, Valmas C, Martinez O, Sanchez F, Basler C. Ebola virus VP24 proteins inhibit the interaction of NPI-1 subfamily karyopherin alpha proteins with activated STAT1. J Virol. 2007;81:13469-77 pubmed
  6. Sun C, Yang W, Tu L, Musser S. Single-molecule measurements of importin alpha/cargo complex dissociation at the nuclear pore. Proc Natl Acad Sci U S A. 2008;105:8613-8 pubmed publisher
    ..These data are consistent with a model in which Imp alpha/cargo complexes are dissociated on the nucleoplasmic side of the NPC, and this dissociation requires both CAS and RanGTP. ..
  7. Kosugi S, Hasebe M, Entani T, Takayama S, Tomita M, Yanagawa H. Design of peptide inhibitors for the importin alpha/beta nuclear import pathway by activity-based profiling. Chem Biol. 2008;15:940-9 pubmed publisher
    ..These peptide inhibitors provide a useful tool for studying nuclear import events. Moreover, our inhibitor design method should enable the development of potent inhibitors from a peptide seed. ..
  8. Ao Z, Danappa Jayappa K, Wang B, Zheng Y, Kung S, Rassart E, et al. Importin alpha3 interacts with HIV-1 integrase and contributes to HIV-1 nuclear import and replication. J Virol. 2010;84:8650-63 pubmed publisher
    ..Overall, this study demonstrates for the first time that Impalpha3 is an HIV integrase-interacting cofactor that is required for efficient HIV-1 nuclear import and replication in both dividing and nondividing cells. ..
  9. Ganesh K, Adam S, Taylor B, Simpson P, Rada C, Neuberger M. CTNNBL1 is a novel nuclear localization sequence-binding protein that recognizes RNA-splicing factors CDC5L and Prp31. J Biol Chem. 2011;286:17091-102 pubmed publisher
    ..Thus, CTNNBL1 is a novel NLS-binding protein, distinct from karyopherin ?s, with the results suggesting a possible role in the selective intranuclear targeting or interactions of some splicing-associated complexes. ..

More Information

Publications107 found, 100 shown here

  1. Yoshitake K, Tanaka S, Mogushi K, Aihara A, Murakata A, Matsumura S, et al. Importin-?1 as a novel prognostic target for hepatocellular carcinoma. Ann Surg Oncol. 2011;18:2093-103 pubmed publisher
    ..291, P = 0.0191). Because importin-?1 might be closely associated with HCC progression, further analysis should be pursued to evaluate it as a novel prognostic target. ..
  2. Chan C, Zhang S, Rousset R, Wharton K. Drosophila Naked cuticle (Nkd) engages the nuclear import adaptor Importin-alpha3 to antagonize Wnt/beta-catenin signaling. Dev Biol. 2008;318:17-28 pubmed publisher
    ..Our results provide further support for the hypothesis that Nkd inhibits nuclear step(s) in Wnt/beta-catenin signaling and broaden our understanding of signaling pathways that engage the nuclear import machinery. ..
  3. Sakai M, Sohda M, Miyazaki T, Suzuki S, Sano A, Tanaka N, et al. Significance of karyopherin-{alpha} 2 (KPNA2) expression in esophageal squamous cell carcinoma. Anticancer Res. 2010;30:851-6 pubmed
    ..KPNA2 expression is associated with poor differentiation, tumor invasiveness, and tumor proliferation in ESCC. ..
  4. Tabb M, Tongaonkar P, Vu L, Nomura M. Evidence for separable functions of Srp1p, the yeast homolog of importin alpha (Karyopherin alpha): role for Srp1p and Sts1p in protein degradation. Mol Cell Biol. 2000;20:6062-73 pubmed
    ..These results suggest a role for Srp1p in regulation of protein degradation separate from its well-established role as the NLS receptor...
  5. Wang C, Chien K, Wang C, Liu H, Cheng C, Chang Y, et al. Quantitative proteomics reveals regulation of karyopherin subunit alpha-2 (KPNA2) and its potential novel cargo proteins in nonsmall cell lung cancer. Mol Cell Proteomics. 2012;11:1105-22 pubmed publisher
    ..Our results collectively demonstrate the utility of quantitative proteomic approaches and provide a fundamental platform to further explore the biological roles of KPNA2 in nonsmall cell lung cancer. ..
  6. Kohler M, Gorlich D, Hartmann E, Franke J. Adenoviral E1A protein nuclear import is preferentially mediated by importin alpha3 in vitro. Virology. 2001;289:186-91 pubmed
    ..Competition with nucleoplasmin suggests that importin alpha3 is the most efficient import mediator of E1A. ..
  7. Young J, Major A, Miyamoto Y, Loveland K, Jans D. Distinct effects of importin ?2 and ?4 on Oct3/4 localization and expression in mouse embryonic stem cells. FASEB J. 2011;25:3958-65 pubmed publisher
    ..These findings implicate IMP?2 and IMP?4 in specific but distinct roles in the fate choice between pluripotency and commitment to differentiation. ..
  8. Gluz O, Wild P, Meiler R, Diallo Danebrock R, Ting E, Mohrmann S, et al. Nuclear karyopherin alpha2 expression predicts poor survival in patients with advanced breast cancer irrespective of treatment intensity. Int J Cancer. 2008;123:1433-8 pubmed publisher
    ..KPNA2 expression may be also considered as a marker for global chemoresistance, which can not be overcome by conventional dose-modification of chemotherapy in advanced breast cancer. ..
  9. Depping R, Steinhoff A, Schindler S, Friedrich B, Fagerlund R, Metzen E, et al. Nuclear translocation of hypoxia-inducible factors (HIFs): involvement of the classical importin alpha/beta pathway. Biochim Biophys Acta. 2008;1783:394-404 pubmed publisher
    ..In contrast, the supposed N-terminal NLS is not effective. Our findings provide new insight into the mechanism of the regulation of nuclear transport of hypoxia-inducible factors. ..
  10. van der Watt P, Ngarande E, Leaner V. Overexpression of Kpn?1 and Kpn?2 importin proteins in cancer derives from deregulated E2F activity. PLoS ONE. 2011;6:e27723 pubmed publisher
    ..In conclusion, this study is a first to show that elevated Kpn?1 and Kpn?2 expression in cancer cells correlates with altered transcriptional regulation associated with deregulated E2F/Rb activities. ..
  11. Li X, Sun L, Jin Y. Identification of karyopherin-alpha 2 as an Oct4 associated protein. J Genet Genomics. 2008;35:723-8 pubmed publisher
    ..Thus, our data suggest that Oct4 nuclear localization may be mediated by its interaction with KPNA-2. ..
  12. McBride K, Banninger G, McDonald C, Reich N. Regulated nuclear import of the STAT1 transcription factor by direct binding of importin-alpha. EMBO J. 2002;21:1754-63 pubmed
    ..This result may play a role in localizing STAT1 to its destination in the nucleus, and in releasing importin-alpha5 from STAT1 for recycling back to the cytoplasm. ..
  13. Behrens P, Brinkmann U, Wellmann A. CSE1L/CAS: its role in proliferation and apoptosis. Apoptosis. 2003;8:39-44 pubmed
  14. Fontes M, Teh T, Toth G, John A, Pavo I, Jans D, et al. Role of flanking sequences and phosphorylation in the recognition of the simian-virus-40 large T-antigen nuclear localization sequences by importin-alpha. Biochem J. 2003;375:339-49 pubmed
  15. Jensen J, Munksgaard P, Sørensen C, Fristrup N, Birkenkamp Demtroder K, Ulhøi B, et al. High expression of karyopherin-?2 defines poor prognosis in non-muscle-invasive bladder cancer and in patients with invasive bladder cancer undergoing radical cystectomy. Eur Urol. 2011;59:841-8 pubmed publisher
    ..A high KPNA2 expression was correlated with a higher risk of visceral metastasis rather than lymphatic spread. KPNA2 expression is a marker for progression of NMIBC and a prognostic marker in patients undergoing RC. ..
  16. Dahl E, Kristiansen G, Gottlob K, Klaman I, Ebner E, Hinzmann B, et al. Molecular profiling of laser-microdissected matched tumor and normal breast tissue identifies karyopherin alpha2 as a potential novel prognostic marker in breast cancer. Clin Cancer Res. 2006;12:3950-60 pubmed
    ..Gene expression profiling of laser-microdissected breast cancer tissue revealed novel genes that may represent potential molecular targets for breast cancer therapy and prediction of outcome. ..
  17. Tahara K, Takagi M, Ohsugi M, Sone T, Nishiumi F, Maeshima K, et al. Importin-beta and the small guanosine triphosphatase Ran mediate chromosome loading of the human chromokinesin Kid. J Cell Biol. 2008;180:493-506 pubmed publisher
    ..Thus, this study demonstrates a novel nucleocytoplasmic transport factor-mediated mechanism for targeting proteins to mitotic chromosomes. ..
  18. Nitahara Kasahara Y, Kamata M, Yamamoto T, Zhang X, Miyamoto Y, Muneta K, et al. Novel nuclear import of Vpr promoted by importin alpha is crucial for human immunodeficiency virus type 1 replication in macrophages. J Virol. 2007;81:5284-93 pubmed
    ..This study suggests the possibility that the binding of Vpr to importin alpha, preceding a novel nuclear import process, is a potential target for therapeutic intervention. ..
  19. Theodore M, Kawai Y, Yang J, Kleshchenko Y, Reddy S, Villalta F, et al. Multiple nuclear localization signals function in the nuclear import of the transcription factor Nrf2. J Biol Chem. 2008;283:8984-94 pubmed publisher
  20. Hearps A, Jans D. HIV-1 integrase is capable of targeting DNA to the nucleus via an importin alpha/beta-dependent mechanism. Biochem J. 2006;398:475-84 pubmed
    ..These results may not only aid in highlighting potential therapeutic targets for impeding the progression of HIV/AIDS, but may also be relevant for non-viral gene delivery. ..
  21. Kelley J, Talley A, Spencer A, Gioeli D, Paschal B. Karyopherin alpha7 (KPNA7), a divergent member of the importin alpha family of nuclear import receptors. BMC Cell Biol. 2010;11:63 pubmed publisher
    ..These properties suggest that KPNA7 could be specialized for interactions with select NLS-containing proteins, potentially impacting developmental regulation. ..
  22. Reid S, Leung L, Hartman A, Martinez O, Shaw M, Carbonnelle C, et al. Ebola virus VP24 binds karyopherin alpha1 and blocks STAT1 nuclear accumulation. J Virol. 2006;80:5156-67 pubmed
    ..These data suggest that VP24 is likely to be an important virulence determinant that allows EBOV to evade the antiviral effects of IFNs. ..
  23. Boivin S, Hart D. Interaction of the influenza A virus polymerase PB2 C-terminal region with importin alpha isoforms provides insights into host adaptation and polymerase assembly. J Biol Chem. 2011;286:10439-48 pubmed publisher
  24. Kumar G, Shum L, Glaunsinger B. Importin alpha-mediated nuclear import of cytoplasmic poly(A) binding protein occurs as a direct consequence of cytoplasmic mRNA depletion. Mol Cell Biol. 2011;31:3113-25 pubmed publisher
    ..These findings further suggest that cells must carefully calibrate the ratio of PABPC to mRNA, as events that offset this balance can dramatically influence gene expression. ..
  25. Quensel C, Friedrich B, Sommer T, Hartmann E, Kohler M. In vivo analysis of importin alpha proteins reveals cellular proliferation inhibition and substrate specificity. Mol Cell Biol. 2004;24:10246-55 pubmed
    ..Thus, importin alpha3 is the only alpha importin responsible for the classical nuclear import of RCC1 in living cells. ..
  26. Gilchrist D, Rexach M. Molecular basis for the rapid dissociation of nuclear localization signals from karyopherin alpha in the nucleoplasm. J Biol Chem. 2003;278:51937-49 pubmed
    ..NLS-cargo complexes in the nucleoplasm of yeast. We discuss a model whereby Nup2p, Cse1p, and Gsp1p cooperate to establish directionality in the movement of Kap60p and NLS-cargos across the nuclear pore complex. ..
  27. Mason D, Stage D, Goldfarb D. Evolution of the metazoan-specific importin alpha gene family. J Mol Evol. 2009;68:351-65 pubmed publisher
    ..Finally, these results establish a rational basis for a unified nomenclature of the importin alpha gene family. ..
  28. Tseng S, Chang C, Wu K, Teng S. Importin KPNA2 is required for proper nuclear localization and multiple functions of NBS1. J Biol Chem. 2005;280:39594-600 pubmed
    ..Collectively, our results strongly suggest that an interaction with KPNA2 contributes to nuclear localization and multiple tumor suppression functions of the NBS1 complex. ..
  29. Yang S, Takeda A, Fontes M, Harris J, Jans D, Kobe B. Probing the specificity of binding to the major nuclear localization sequence-binding site of importin-alpha using oriented peptide library screening. J Biol Chem. 2010;285:19935-46 pubmed publisher
  30. Zheng M, Tang L, Huang L, Ding H, Liao W, Zeng M, et al. Overexpression of karyopherin-2 in epithelial ovarian cancer and correlation with poor prognosis. Obstet Gynecol. 2010;116:884-91 pubmed publisher
    ..05). KPNA2 may play an important role in the development, differentiation, and carcinogenesis of epithelial ovarian cancer and therefore could be an indicator of poor prognosis for patients with epithelial ovarian cancer. II. ..
  31. Kodiha M, Tran D, Qian C, Morogan A, Presley J, Brown C, et al. Oxidative stress mislocalizes and retains transport factor importin-alpha and nucleoporins Nup153 and Nup88 in nuclei where they generate high molecular mass complexes. Biochim Biophys Acta. 2008;1783:405-18 pubmed
    ..Taken together, our studies link oxidative stress to the proper localization of soluble transport factors and nucleoporins and to changes in the interactions between these proteins. ..
  32. Mateo M, Reid S, Leung L, Basler C, Volchkov V. Ebolavirus VP24 binding to karyopherins is required for inhibition of interferon signaling. J Virol. 2010;84:1169-75 pubmed publisher
    ..We demonstrate that loss of function correlates with loss of binding to KPNalpha proteins. Thus, the VP24 IFN antagonist function requires the ability of VP24 to interact with KPNalpha. ..
  33. Huenniger K, Kramer A, Soom M, Chang I, Kohler M, Depping R, et al. Notch1 signaling is mediated by importins alpha 3, 4, and 7. Cell Mol Life Sci. 2010;67:3187-96 pubmed publisher
    ..siRNA-mediated knockdown experiments showed that importins alpha3, alpha4 (and to a lesser extent, alpha7) mediate nuclear import of NICD and thus are directly involved in Notch signaling. ..
  34. Suzuki T, Yamamoto N, Nonaka M, Hashimoto Y, Matsuda G, Takeshima S, et al. Inhibition of human immunodeficiency virus type 1 (HIV-1) nuclear import via Vpr-Importin alpha interactions as a novel HIV-1 therapy. Biochem Biophys Res Commun. 2009;380:838-43 pubmed publisher
  35. Kelly K, Otchere A, Graham M, Daniel J. Nuclear import of the BTB/POZ transcriptional regulator Kaiso. J Cell Sci. 2004;117:6143-52 pubmed
    ..The identification of a Kaiso NLS thus clarifies the mechanism by which Kaiso translocates to the nucleus to regulate transcription of genes with diverse roles in cell growth and development. ..
  36. Hogarth C, Calanni S, Jans D, Loveland K. Importin alpha mRNAs have distinct expression profiles during spermatogenesis. Dev Dyn. 2006;235:253-62 pubmed
    ..The distinct importin alpha expression patterns are consistent with their having specific roles and transport cargoes during spermatogenesis. ..
  37. Chook Y, Blobel G. Karyopherins and nuclear import. Curr Opin Struct Biol. 2001;11:703-15 pubmed
    ..These karyopherin structures provide valuable insights into understanding the molecular mechanism of nuclear import, especially substrate recognition, substrate release by GTPase and interactions with the nuclear pore complex. ..
  38. Fagerlund R, Melen K, Kinnunen L, Julkunen I. Arginine/lysine-rich nuclear localization signals mediate interactions between dimeric STATs and importin alpha 5. J Biol Chem. 2002;277:30072-8 pubmed
    ..Our results demonstrate that specific NLSs in STATs mediate direct interactions of STAT dimers with importin alpha, which activates the nuclear import process. ..
  39. Forwood J, Jans D. Nuclear import pathway of the telomere elongation suppressor TRF1: inhibition by importin alpha. Biochemistry. 2002;41:9333-40 pubmed
  40. Cabot R, Prather R. Cleavage stage porcine embryos may have differing developmental requirements for karyopherins alpha2 and alpha3. Mol Reprod Dev. 2003;64:292-301 pubmed
    ..This is the first report indicating that mammalian embryos may have differential developmental requirements for specific nuclear trafficking pathways. ..
  41. Melen K, Fagerlund R, Franke J, Kohler M, Kinnunen L, Julkunen I. Importin alpha nuclear localization signal binding sites for STAT1, STAT2, and influenza A virus nucleoprotein. J Biol Chem. 2003;278:28193-200 pubmed
  42. Ems McClung S, Zheng Y, Walczak C. Importin alpha/beta and Ran-GTP regulate XCTK2 microtubule binding through a bipartite nuclear localization signal. Mol Biol Cell. 2004;15:46-57 pubmed
    ..Our data show that importin alpha/beta directly regulates the activity of XCTK2 and that one of the molecular mechanisms of Ran-regulated spindle assembly is identical to that used in classical NLS-driven nuclear transport. ..
  43. Kumar S, Chaturvedi N, Nishi M, Kawata M, Tyagi R. Shuttling components of nuclear import machinery involved in nuclear translocation of steroid receptors exit nucleus via exportin-1/CRM-1* independent pathway. Biochim Biophys Acta. 2004;1691:73-7 pubmed
  44. Tarendeau F, Boudet J, Guilligay D, Mas P, Bougault C, Boulo S, et al. Structure and nuclear import function of the C-terminal domain of influenza virus polymerase PB2 subunit. Nat Struct Mol Biol. 2007;14:229-33 pubmed
    ..The domain contains three surface residues implicated in adaptation from avian to mammalian hosts. One of these tethers the NLS-containing peptide to the core of the domain in the unbound state. ..
  45. Yeung P, Chen L, Tsai S, Zhang A, Chen J. Daxx contains two nuclear localization signals and interacts with importin alpha3. J Cell Biochem. 2008;103:456-70 pubmed
    ..Together, these data unveil a molecular mechanism that controls nuclear localization of Daxx and support a nuclear role of Daxx in transcriptional regulation. ..
  46. Ting C, Herman T, Yonekura S, Gao S, Wang J, Serpe M, et al. Tiling of r7 axons in the Drosophila visual system is mediated both by transduction of an activin signal to the nucleus and by mutual repulsion. Neuron. 2007;56:793-806 pubmed
    ..We propose that dActivin is an autocrine signal that restricts R7 growth cone motility, and we demonstrate that it acts in parallel with a paracrine signal that mediates repulsion between R7 terminals. ..
  47. Tarendeau F, Crepin T, Guilligay D, Ruigrok R, Cusack S, Hart D. Host determinant residue lysine 627 lies on the surface of a discrete, folded domain of influenza virus polymerase PB2 subunit. PLoS Pathog. 2008;4:e1000136 pubmed publisher
    ..The identification and structural characterization of these well-defined PB2 domains will help design experiments to elucidate the effects of mutations on polymerase-host factor interactions. ..
  48. Hall M, Griffin C, Simionescu A, Corbett A, Pavlath G. Distinct roles for classical nuclear import receptors in the growth of multinucleated muscle cells. Dev Biol. 2011;357:248-58 pubmed publisher
  49. Noetzel E, Rose M, Bornemann J, Gajewski M, Knuchel R, Dahl E. Nuclear transport receptor karyopherin-?2 promotes malignant breast cancer phenotypes in vitro. Oncogene. 2012;31:2101-14 pubmed publisher
    ..This study gives clear evidence that KPNA2 acts as a novel oncogenic factor in human breast cancer, in vitro. ..
  50. Gousias K, Becker A, Simon M, Niehusmann P. Nuclear karyopherin a2: a novel biomarker for infiltrative astrocytomas. J Neurooncol. 2012;109:545-53 pubmed publisher
    ..004). Survival of glioblastoma patients >5 years was seen only in those with KPNA2 expression levels ?1 % (p = 0.014). KPNA2 expression may have potential as a novel diagnostic and prognostic biomarker for astrocytic gliomas. ..
  51. Lindsay M, Plafker K, Smith A, Clurman B, Macara I. Npap60/Nup50 is a tri-stable switch that stimulates importin-alpha:beta-mediated nuclear protein import. Cell. 2002;110:349-60 pubmed
    ..These results identify Npap60 as a cofactor for importin-alpha:beta nuclear import and as a previously unidentified subunit of the importin complex. ..
  52. Giarre M, Török I, Schmitt R, Gorjanacz M, Kiss I, Mechler B. Patterns of importin-alpha expression during Drosophila spermatogenesis. J Struct Biol. 2002;140:279-90 pubmed
    ..These data indicate that each Imp-alpha protein carries during Drosophila spermatogenesis distinct, albeit overlapping, functions that may involve nuclear import of proteins, microtubule organisation, and other yet unknown processes. ..
  53. Hachet V, Kocher T, Wilm M, Mattaj I. Importin alpha associates with membranes and participates in nuclear envelope assembly in vitro. EMBO J. 2004;23:1526-35 pubmed
    ..Unlike other functions of Importin alpha, this membrane-associated activity does not require interaction with NLS proteins. ..
  54. Thompson K, Otis K, Chen D, Zhao Y, O Dell T, Martin K. Synapse to nucleus signaling during long-term synaptic plasticity; a role for the classical active nuclear import pathway. Neuron. 2004;44:997-1009 pubmed publisher
  55. Cros J, Garcia Sastre A, Palese P. An unconventional NLS is critical for the nuclear import of the influenza A virus nucleoprotein and ribonucleoprotein. Traffic. 2005;6:205-13 pubmed
    ..Finally, viral replication could be specifically inhibited by a membrane-permeable peptide containing the unconventional NLS, confirming the crucial role of this signal during the replicative cycle of the virus. ..
  56. Riddick G, Macara I. A systems analysis of importin-{alpha}-{beta} mediated nuclear protein import. J Cell Biol. 2005;168:1027-38 pubmed
    ..The model revealed that inhibition by RCC1 is caused by sequestration of nuclear Ran. Inhibition by Impbeta results from depletion nuclear RanGTP, and, in support of this mechanism, expression of mRFP-Ran reversed the inhibition. ..
  57. Huang S, Huang S, Wang S, Liu P. Importin alpha1 is involved in the nuclear localization of Zac1 and the induction of p21WAF1/CIP1 by Zac1. Biochem J. 2007;402:359-66 pubmed
    ..Finally, our results indicate that the association of Zac1 with importin alpha1 is also involved in regulating the transactivation activity of Zac1 on the p21WAF1/CIP1 gene and protein expression. ..
  58. Yasuhara N, Shibazaki N, Tanaka S, Nagai M, Kamikawa Y, Oe S, et al. Triggering neural differentiation of ES cells by subtype switching of importin-alpha. Nat Cell Biol. 2007;9:72-9 pubmed
    ..This is the first study to propose that transport factors should be considered as major players in cell-fate determination. ..
  59. Umegaki N, Tamai K, Nakano H, Moritsugu R, Yamazaki T, Hanada K, et al. Differential regulation of karyopherin alpha 2 expression by TGF-beta1 and IFN-gamma in normal human epidermal keratinocytes: evident contribution of KPNA2 for nuclear translocation of IRF-1. J Invest Dermatol. 2007;127:1456-64 pubmed
    ..Our data suggest that KPNA2 may play an important role in the signal-transduction pathways that regulate epidermal proliferation and differentiation. ..
  60. Frieman M, Yount B, Heise M, Kopecky Bromberg S, Palese P, Baric R. Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane. J Virol. 2007;81:9812-24 pubmed
    ..We discuss the likely implications of these data on SARS-CoV replication and pathogenesis. ..
  61. Dankof A, Fritzsche F, Dahl E, Pahl S, Wild P, Dietel M, et al. KPNA2 protein expression in invasive breast carcinoma and matched peritumoral ductal carcinoma in situ. Virchows Arch. 2007;451:877-81 pubmed
    ..Additionally, KPNA2 is overexpressed in DCIS, particularly high grade lesions, which emphasizes its potential role in carcinogenesis of invasive breast carcinomas. ..
  62. Fagerlund R, Melen K, Cao X, Julkunen I. NF-kappaB p52, RelB and c-Rel are transported into the nucleus via a subset of importin alpha molecules. Cell Signal. 2008;20:1442-51 pubmed publisher
    ..Moreover, we show that the nuclear import of p52/RelB heterodimers is mediated exclusively by the NLS of RelB. In addition, we found that the NLS of p52 mediates the nuclear import of p52/p65 heterodimers. ..
  63. Lai K, Zhao Y, Ch ng T, Martin K. Importin-mediated retrograde transport of CREB2 from distal processes to the nucleus in neurons. Proc Natl Acad Sci U S A. 2008;105:17175-80 pubmed publisher
    ..Together, our findings indicate that CREB2 is a novel cargo of importin alpha that translocates from distal synaptic sites to the nucleus after stimuli that induce LTD of neuronal synapses. ..
  64. Tejomurtula J, Lee K, Tripurani S, Smith G, Yao J. Role of importin alpha8, a new member of the importin alpha family of nuclear transport proteins, in early embryonic development in cattle. Biol Reprod. 2009;81:333-42 pubmed publisher
    ..These results suggest that KPNA7 may have an important role in the transport of essential nuclear proteins required for early embryogenesis. ..
  65. Kosugi S, Hasebe M, Tomita M, Yanagawa H. Systematic identification of cell cycle-dependent yeast nucleocytoplasmic shuttling proteins by prediction of composite motifs. Proc Natl Acad Sci U S A. 2009;106:10171-6 pubmed publisher
    ..The application of this strategy to other functional linear motifs should be useful in systematic studies of protein-protein networks. ..
  66. Nardozzi J, Wenta N, Yasuhara N, Vinkemeier U, Cingolani G. Molecular basis for the recognition of phosphorylated STAT1 by importin alpha5. J Mol Biol. 2010;402:83-100 pubmed publisher
  67. Hu J, Wang F, Yuan Y, Zhu X, Wang Y, Zhang Y, et al. Novel importin-alpha family member Kpna7 is required for normal fertility and fecundity in the mouse. J Biol Chem. 2010;285:33113-22 pubmed publisher
    ..Biochemical analysis showed that KPNA7 interacts with KPNB1 (importin-?1). In summary, we identified a novel Kpna7 gene that is required for normal fertility and fecundity. ..
  68. Pelaez R, Fernández García P, Herrero P, Moreno F. Nuclear import of the yeast hexokinase 2 protein requires ?/?-importin-dependent pathway. J Biol Chem. 2012;287:3518-29 pubmed publisher
    ..It is also demonstrated that Hxk2 nuclear import and its binding to Kap95 and Kap60 depend on the Gsp1-GTP/GDP protein levels. Thus, our study uncovers Hxk2 as a new cargo for the ?/?-importin pathway of S. cerevisiae. ..
  69. Tekotte H, Berdnik D, Torok T, Buszczak M, Jones L, Cooley L, et al. Dcas is required for importin-alpha3 nuclear export and mechano-sensory organ cell fate specification in Drosophila. Dev Biol. 2002;244:396-406 pubmed
    ..We propose that mutations in house keeping genes often cause specific developmental phenotypes, such as those observed in many human genetic disorders. ..
  70. Schatz C, Santarella R, Hoenger A, Karsenti E, Mattaj I, Gruss O, et al. Importin alpha-regulated nucleation of microtubules by TPX2. EMBO J. 2003;22:2060-70 pubmed
    ..The data suggest that the critical early function in spindle formation regulated by importin alpha is TPX2-mediated microtubule nucleation. ..
  71. Mason D, Mathe E, Fleming R, Goldfarb D. The Drosophila melanogaster importin alpha3 locus encodes an essential gene required for the development of both larval and adult tissues. Genetics. 2003;165:1943-58 pubmed
    ..These results are consistent with the view that the importin alpha's have both overlapping and distinct functions and that their role in animal development involves the spatial and temporal control of their expression. ..
  72. Furuta M, Kose S, Koike M, Shimi T, Hiraoka Y, Yoneda Y, et al. Heat-shock induced nuclear retention and recycling inhibition of importin alpha. Genes Cells. 2004;9:429-41 pubmed
    ..This suggests a new regulatory mechanism for the adaptation of cells to environmental changes, such as heat-shock. ..
  73. Wendler P, Lehmann A, Janek K, Baumgart S, Enenkel C. The bipartite nuclear localization sequence of Rpn2 is required for nuclear import of proteasomal base complexes via karyopherin alphabeta and proteasome functions. J Biol Chem. 2004;279:37751-62 pubmed
    ..Our data support the model by which nuclear 26 S proteasomes are assembled from subcomplexes imported by karyopherin alphabeta. ..
  74. Kamikubo Y, Sakaguchi N, Shikata K, Furuta M, Miyamoto Y, Imamoto N, et al. Specific monoclonal antibody against nuclear import factor, importin alpha1/Rch1. Hybrid Hybridomics. 2004;23:301-4 pubmed
  75. Fagerlund R, Kinnunen L, Kohler M, Julkunen I, Melen K. NF-{kappa}B is transported into the nucleus by importin {alpha}3 and importin {alpha}4. J Biol Chem. 2005;280:15942-51 pubmed
    ..The present study demonstrates that the nuclear import of NF-kappaB is a highly regulated process mediated by a subset of importin alpha molecules. ..
  76. Kamata M, Nitahara Kasahara Y, Miyamoto Y, Yoneda Y, Aida Y. Importin-alpha promotes passage through the nuclear pore complex of human immunodeficiency virus type 1 Vpr. J Virol. 2005;79:3557-64 pubmed
    ..These observations indicate that importin-alpha functions as a mediator for the nuclear entry of Vpr. ..
  77. Li H, Tschudi C. Novel and essential subunits in the 300-kilodalton nuclear cap binding complex of Trypanosoma brucei. Mol Cell Biol. 2005;25:2216-26 pubmed publisher
    ..brucei CBC by RNA interference demonstrated an essential function at an early step in trans-splicing. Thus, our studies are consistent with the CBC providing a mechanistic link between cap 4 modifications and trans-splicing...
  78. Cook A, Fernandez E, Lindner D, Ebert J, Schlenstedt G, Conti E. The structure of the nuclear export receptor Cse1 in its cytosolic state reveals a closed conformation incompatible with cargo binding. Mol Cell. 2005;18:355-67 pubmed
    ..Mutations that destabilize the N- to C-terminal interaction uncouple importin alpha and Ran binding, suggesting that the closed conformation prevents association with importin alpha. ..
  79. Faul C, Huttelmaier S, Oh J, Hachet V, Singer R, Mundel P. Promotion of importin alpha-mediated nuclear import by the phosphorylation-dependent binding of cargo protein to 14-3-3. J Cell Biol. 2005;169:415-24 pubmed
    ..They provide a molecular explanation for the phosphorylation-dependent nuclear import of nuclear localization signal-containing cargo proteins. ..
  80. Ma J, Cao X. Regulation of Stat3 nuclear import by importin alpha5 and importin alpha7 via two different functional sequence elements. Cell Signal. 2006;18:1117-26 pubmed
    ..A model for Stat3 nuclear translocation is proposed based on these data. ..
  81. Friedrich B, Quensel C, Sommer T, Hartmann E, Kohler M. Nuclear localization signal and protein context both mediate importin alpha specificity of nuclear import substrates. Mol Cell Biol. 2006;26:8697-709 pubmed
    ..In vitro binding studies and nuclear import assays revealed that both NLS and protein context contribute to the specificity of importin alpha binding and transport. ..
  82. Ao Z, Huang G, Yao H, Xu Z, Labine M, Cochrane A, et al. Interaction of human immunodeficiency virus type 1 integrase with cellular nuclear import receptor importin 7 and its impact on viral replication. J Biol Chem. 2007;282:13456-67 pubmed
    ..5-3.5-fold inhibition of HIV infection. Altogether, our results indicate that HIV-1 IN specifically interacts with Imp7, and this viral/cellular protein interaction contributes to efficient HIV-1 infection. ..
  83. Hutten S, Flotho A, Melchior F, Kehlenbach R. The Nup358-RanGAP complex is required for efficient importin alpha/beta-dependent nuclear import. Mol Biol Cell. 2008;19:2300-10 pubmed publisher
    ..Together, these data suggest a dual function of the Nup358-RanGAP1 complex as a coordinator of importin beta recycling and reformation of novel import complexes. ..
  84. Dias S, Wilson K, Rojas K, Ambrosio A, Cerione R. The molecular basis for the regulation of the cap-binding complex by the importins. Nat Struct Mol Biol. 2009;16:930-7 pubmed publisher
    ..Together, these studies enable us to propose a model describing how importin-beta stimulates the dissociation of capped RNA from the CBC in the cytosol following its nuclear export. ..
  85. Ogawa Y, Miyamoto Y, Asally M, Oka M, Yasuda Y, Yoneda Y. Two isoforms of Npap60 (Nup50) differentially regulate nuclear protein import. Mol Biol Cell. 2010;21:630-8 pubmed publisher
    ..This study provides novel evidence that nucleoporin expression levels regulate nuclear import efficiency. ..
  86. Kohler M, Buchwalow I, Alexander G, Christiansen M, Shagdarsuren E, Samoilova V, et al. Increased importin alpha protein expression in diabetic nephropathy. Kidney Int. 2001;60:2263-73 pubmed
    ..The signaling pathways appear differentially regulated in glomeruli, proximal, and distal tubules. The enhanced nuclear transport may participate in increased gene expression and nephrosclerosis in diabetes. ..
  87. Kalab P, Weis K, Heald R. Visualization of a Ran-GTP gradient in interphase and mitotic Xenopus egg extracts. Science. 2002;295:2452-6 pubmed
  88. Harreman M, Hodel M, Fanara P, Hodel A, Corbett A. The auto-inhibitory function of importin alpha is essential in vivo. J Biol Chem. 2003;278:5854-63 pubmed
    ..We propose a model where the auto-inhibitory activity of importin alpha is required for NLS-cargo release and the subsequent Cse1p-dependent recycling of importin alpha to the cytoplasm. ..
  89. Fontes M, Teh T, Jans D, Brinkworth R, Kobe B. Structural basis for the specificity of bipartite nuclear localization sequence binding by importin-alpha. J Biol Chem. 2003;278:27981-7 pubmed
  90. Zannini L, Lecis D, Lisanti S, Benetti R, Buscemi G, Schneider C, et al. Karyopherin-alpha2 protein interacts with Chk2 and contributes to its nuclear import. J Biol Chem. 2003;278:42346-51 pubmed
    ..Finally, co-transfection experiments with green fluorescent protein (GFP)-Chk2 and wild type or mutant KPNA-2 confirmed the role of KPNA-2 in nuclear import of Chk2. ..
  91. Cassany A, Guillemain G, Klein C, Dalet V, Brot Laroche E, Leturque A. A karyopherin alpha2 nuclear transport pathway is regulated by glucose in hepatic and pancreatic cells. Traffic. 2004;5:10-9 pubmed
    ..Thus, extracellular glucose regulates a nuclear transport pathway by increasing the nuclear efflux and shuttling of karyopherin alpha2 in cells in which glucose can stimulate the transcription of sugar-responsive genes. ..
  92. Gorjanacz M, Török I, Pomozi I, Garab G, Szlanka T, Kiss I, et al. Domains of Importin-alpha2 required for ring canal assembly during Drosophila oogenesis. J Struct Biol. 2006;154:27-41 pubmed
    ..Thus, we propose that mutations in NLS and CAS binding domains affect the deposition of Kelch onto the ring canals and prevent the association of Imp-alpha2 with a negative regulator of Kelch function. ..