This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Palmeri, D.
Right arrow Articles by Malim, M. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Palmeri, D.
Right arrow Articles by Malim, M. H.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 1999, p. 1218-1225, Vol. 19, No. 2
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Importin beta  Can Mediate the Nuclear Import of an Arginine-Rich Nuclear Localization Signal in the Absence of Importin alpha

Diana Palmeri1 and Michael H. Malim2,3,4,*

Cell and Molecular Biology Graduate Group,1 Departments of Microbiology2 and Medicine,3 and Howard Hughes Medical Institute,4 University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148

Received 17 August 1998/Returned for modification 14 October 1998/Accepted 27 October 1998

The import of proteins into the nucleus is dependent on cis-acting targeting sequences, nuclear localization signals (NLSs), and members of the nuclear transport receptor (importin-beta -like) superfamily. The most extensively characterized import pathway, often termed the classical pathway, is utilized by many basic-type (lysine-rich) NLSs and requires an additional component, importin alpha , to serve as a bridge between the NLS and the import receptor importin beta . More recently, it has become clear that a variety of proteins enter the nucleus via alternative import receptors and that their NLSs bind directly to those receptors. By using the digitonin-permeabilized cell system for protein import in vitro, we have defined the import pathway for the Rex protein of human T-cell leukemia virus type 1. Interestingly, the arginine-rich NLS of Rex uses importin beta  for import but does so by a mechanism that is importin alpha  independent. Based on the ability of the Rex NLS to inhibit the import of the lysine-rich NLS of T antigen and of both NLSs to be inhibited by the domain of importin alpha  that binds importin beta  (the IBB domain), we infer that the Rex NLS interacts with importin beta  directly. In addition, and in keeping with other receptor-mediated nuclear import pathways, Rex import is dependent on the integrity of the Ran GTPase cycle. Based on these results, we suggest that importin beta  can mediate the nuclear import of arginine-rich NLSs directly, or lysine-rich NLSs through the action of importin alpha .

* Corresponding author. Mailing address: Departments of Microbiology and Medicine, University of Pennsylvania Medical School, Philadelphia, PA 19104-6148. Phone: (215) 573-3493. Fax: (215) 573-2172. E-mail: malim{at}mail.med.upenn.edu.

Molecular and Cellular Biology, February 1999, p. 1218-1225, Vol. 19, No. 2
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Sato, H., Maquat, L. E. (2009). Remodeling of the pioneer translation initiation complex involves translation and the karyopherin importin {beta}. Genes Dev. 23: 2537-2550 [Abstract] [Full Text]  
  • Itoh, S., Kim, H. W., Nakagawa, O., Ozumi, K., Lessner, S. M., Aoki, H., Akram, K., McKinney, R. D., Ushio-Fukai, M., Fukai, T. (2008). Novel Role of Antioxidant-1 (Atox1) as a Copper-dependent Transcription Factor Involved in Cell Proliferation. J. Biol. Chem. 283: 9157-9167 [Abstract] [Full Text]  
  • Philips, A. S., Kwok, J. C., Chong, B. H. (2007). Analysis of the Signals and Mechanisms Mediating Nuclear Trafficking of GATA-4: LOSS OF DNA BINDING IS ASSOCIATED WITH LOCALIZATION IN INTRANUCLEAR SPECKLES. J. Biol. Chem. 282: 24915-24927 [Abstract] [Full Text]  
  • Chu, H.-Y., Ohtoshi, A. (2007). Cloning and Functional Analysis of Hypothalamic Homeobox Gene Bsx1a and Its Isoform, Bsx1b. Mol. Cell. Biol. 27: 3743-3749 [Abstract] [Full Text]  
  • Tsuji, T., Sheehy, N., Gautier, V. W., Hayakawa, H., Sawa, H., Hall, W. W. (2007). The Nuclear Import of the Human T Lymphotropic Virus Type I (HTLV-1) Tax Protein Is Carrier- and Energy-independent. J. Biol. Chem. 282: 13875-13883 [Abstract] [Full Text]  
  • Ao, Z., Huang, G., Yao, H., Xu, Z., Labine, M., Cochrane, A. W., Yao, X. (2007). Interaction of Human Immunodeficiency Virus Type 1 Integrase with Cellular Nuclear Import Receptor Importin 7 and Its Impact on Viral Replication. J. Biol. Chem. 282: 13456-13467 [Abstract] [Full Text]  
  • Hsu, S.-C., Hung, M.-C. (2007). Characterization of a Novel Tripartite Nuclear Localization Sequence in the EGFR Family. J. Biol. Chem. 282: 10432-10440 [Abstract] [Full Text]  
  • Deng, T., Engelhardt, O. G., Thomas, B., Akoulitchev, A. V., Brownlee, G. G., Fodor, E. (2006). Role of Ran Binding Protein 5 in Nuclear Import and Assembly of the Influenza Virus RNA Polymerase Complex. J. Virol. 80: 11911-11919 [Abstract] [Full Text]  
  • Verhagen, J., Donnelly, M., Elliott, G. (2006). Characterization of a Novel Transferable CRM-1-Independent Nuclear Export Signal in a Herpesvirus Tegument Protein That Shuttles between the Nucleus and Cytoplasm.. J. Virol. 80: 10021-10035 [Abstract] [Full Text]  
  • Arnold, M., Nath, A., Wohlwend, D., Kehlenbach, R. H. (2006). Transportin Is a Major Nuclear Import Receptor for c-Fos: A NOVEL MODE OF CARGO INTERACTION. J. Biol. Chem. 281: 5492-5499 [Abstract] [Full Text]  
  • Singhal, P. K., Kumar, P. R., Rao, M. R. K. S., Kyasani, M., Mahalingam, S. (2006). Simian Immunodeficiency Virus Vpx Is Imported into the Nucleus via Importin Alpha-Dependent and -Independent Pathways. J. Virol. 80: 526-536 [Abstract] [Full Text]  
  • Yasmin, R., Williams, R. M., Xu, M., Noy, N. (2005). Nuclear Import of the Retinoid X Receptor, the Vitamin D Receptor, and Their Mutual Heterodimer. J. Biol. Chem. 280: 40152-40160 [Abstract] [Full Text]  
  • Jeney, V., Itoh, S., Wendt, M., Gradek, Q., Ushio-Fukai, M., Harrison, D. G., Fukai, T. (2005). Role of Antioxidant-1 in Extracellular Superoxide Dismutase Function and Expression. Circ. Res. 96: 723-729 [Abstract] [Full Text]  
  • Bhatti, M. M., Sullivan, W. J. Jr. (2005). Histone Acetylase GCN5 Enters the Nucleus via Importin-{alpha} in Protozoan Parasite Toxoplasma gondii. J. Biol. Chem. 280: 5902-5908 [Abstract] [Full Text]  
  • Schaley, J. E., Polonskaia, M., Hearing, P. (2005). The Adenovirus E4-6/7 Protein Directs Nuclear Localization of E2F-4 via an Arginine-Rich Motif. J. Virol. 79: 2301-2308 [Abstract] [Full Text]  
  • Garbitt, R. A., Bone, K. R., Parent, L. J. (2004). Insertion of a Classical Nuclear Import Signal into the Matrix Domain of the Rous Sarcoma Virus Gag Protein Interferes with Virus Replication. J. Virol. 78: 13534-13542 [Abstract] [Full Text]  
  • Quensel, C., Friedrich, B., Sommer, T., Hartmann, E., Kohler, M. (2004). In Vivo Analysis of Importin {alpha} Proteins Reveals Cellular Proliferation Inhibition and Substrate Specificity. Mol. Cell. Biol. 24: 10246-10255 [Abstract] [Full Text]  
  • Gershburg, E., Marschall, M., Hong, K., Pagano, J. S. (2004). Expression and Localization of the Epstein-Barr Virus-Encoded Protein Kinase. J. Virol. 78: 12140-12146 [Abstract] [Full Text]  
  • Maertens, G., Cherepanov, P., Debyser, Z., Engelborghs, Y., Engelman, A. (2004). Identification and Characterization of a Functional Nuclear Localization Signal in the HIV-1 Integrase Interactor LEDGF/p75. J. Biol. Chem. 279: 33421-33429 [Abstract] [Full Text]  
  • Hasper, A. A., Trindade, L. M., van der Veen, D., van Ooyen, A. J. J., de Graaff, L. H. (2004). Functional analysis of the transcriptional activator XlnR from Aspergillus niger. Microbiology 150: 1367-1375 [Abstract] [Full Text]  
  • Chkheidze, A. N., Liebhaber, S. A. (2003). A Novel Set of Nuclear Localization Signals Determine Distributions of the {alpha}CP RNA-Binding Proteins. Mol. Cell. Biol. 23: 8405-8415 [Abstract] [Full Text]  
  • Lee, S. J., Sekimoto, T., Yamashita, E., Nagoshi, E., Nakagawa, A., Imamoto, N., Yoshimura, M., Sakai, H., Chong, K. T., Tsukihara, T., Yoneda, Y. (2003). The Structure of Importin-{beta} Bound to SREBP-2: Nuclear Import of a Transcription Factor. Science 302: 1571-1575 [Abstract] [Full Text]  
  • Igarashi, N., Okada, T., Hayashi, S., Fujita, T., Jahangeer, S., Nakamura, S.-i. (2003). Sphingosine Kinase 2 Is a Nuclear Protein and Inhibits DNA Synthesis. J. Biol. Chem. 278: 46832-46839 [Abstract] [Full Text]  
  • Harley, V. R., Layfield, S., Mitchell, C. L., Forwood, J. K., John, A. P., Briggs, L. J., McDowall, S. G., Jans, D. A. (2003). Defective importin {beta} recognition and nuclear import of the sex-determining factor SRY are associated with XY sex-reversing mutations. Proc. Natl. Acad. Sci. USA 100: 7045-7050 [Abstract] [Full Text]  
  • Yun, C. Y., Velazquez-Dones, A. L., Lyman, S. K., Fu, X.-D. (2003). Phosphorylation-dependent and -independent Nuclear Import of RS Domain-containing Splicing Factors and Regulators. J. Biol. Chem. 278: 18050-18055 [Abstract] [Full Text]  
  • Nikolaev, I., Cochet, M.-F., Felenbok, B. (2003). Nuclear Import of Zinc Binuclear Cluster Proteins Proceeds through Multiple, Overlapping Transport Pathways. Eukaryot Cell 2: 209-221 [Abstract] [Full Text]  
  • Lam, M. H. C., Thomas, R. J., Loveland, K. L., Schilders, S., Gu, M., Martin, T. J., Gillespie, M. T., Jans, D. A. (2002). Nuclear Transport of Parathyroid Hormone (PTH)-Related Protein Is Dependent on Microtubules. Mol. Endocrinol. 16: 390-401 [Abstract] [Full Text]  
  • Macara, I. G. (2001). Transport into and out of the Nucleus. Microbiol. Mol. Biol. Rev. 65: 570-594 [Abstract] [Full Text]  
  • Forwood, J. K., Harley, V., Jans, D. A. (2001). The C-terminal Nuclear Localization Signal of the Sex-determining Region Y (SRY) High Mobility Group Domain Mediates Nuclear Import through Importin beta 1. J. Biol. Chem. 276: 46575-46582 [Abstract] [Full Text]  
  • Nagoshi, E., Yoneda, Y. (2001). Dimerization of Sterol Regulatory Element-Binding Protein 2 via the Helix-Loop-Helix-Leucine Zipper Domain Is a Prerequisite for Its Nuclear Localization Mediated by Importin {beta}. Mol. Cell. Biol. 21: 2779-2789 [Abstract] [Full Text]  
  • Kurisaki, A., Kose, S., Yoneda, Y., Heldin, C.-H., Moustakas, A. (2001). Transforming Growth Factor-{beta} Induces Nuclear Import of Smad3 in an Importin-{beta}1 and Ran-dependent Manner. Mol. Biol. Cell 12: 1079-1091 [Abstract] [Full Text]  
  • Donnelly, M., Elliott, G. (2001). Nuclear Localization and Shuttling of Herpes Simplex Virus Tegument Protein VP13/14. J. Virol. 75: 2566-2574 [Abstract] [Full Text]  
  • Nam, Y.-S., Petrovic, A., Jeong, K.-S., Venkatesan, S. (2001). Exchange of the Basic Domain of Human Immunodeficiency Virus Type 1 Rev for a Polyarginine Stretch Expands the RNA Binding Specificity, and a Minimal Arginine Cluster Is Required for Optimal RRE RNA Binding Affinity, Nuclear Accumulation, and trans-Activation. J. Virol. 75: 2957-2971 [Abstract] [Full Text]  
  • Yoshida, K., Blobel, G. (2001). The Karyopherin Kap142p/Msn5p Mediates Nuclear Import and Nuclear Export of Different Cargo Proteins. JCB 152: 729-740 [Abstract] [Full Text]  
  • Sherman, M. P., de Noronha, C. M. C., Heusch, M. I., Greene, S., Greene, W. C. (2001). Nucleocytoplasmic Shuttling by Human Immunodeficiency Virus Type 1 Vpr. J. Virol. 75: 1522-1532 [Abstract] [Full Text]  
  • Mahalingam, S., Van Tine, B., Santiago, M. L., Gao, F., Shaw, G. M., Hahn, B. H. (2001). Functional Analysis of the Simian Immunodeficiency Virus Vpx Protein: Identification of Packaging Determinants and a Novel Nuclear Targeting Domain. J. Virol. 75: 362-374 [Abstract] [Full Text]  
  • Bogerd, H. P., Wiegand, H. L., Yang, J., Cullen, B. R. (2000). Mutational Definition of Functional Domains within the Rev Homolog Encoded by Human Endogenous Retrovirus K. J. Virol. 74: 9353-9361 [Abstract] [Full Text]  
  • Ojala, P. M., Sodeik, B., Ebersold, M. W., Kutay, U., Helenius, A. (2000). Herpes Simplex Virus Type 1 Entry into Host Cells: Reconstitution of Capsid Binding and Uncoating at the Nuclear Pore Complex In Vitro. Mol. Cell. Biol. 20: 4922-4931 [Abstract] [Full Text]  
  • Sander, T. L., Haas, A. L., Peterson, M. J., Morris, J. F. (2000). Identification of a Novel SCAN Box-related Protein That Interacts with MZF1B. THE LEUCINE-RICH SCAN BOX MEDIATES HETERO- AND HOMOPROTEIN ASSOCIATIONS. J. Biol. Chem. 275: 12857-12867 [Abstract] [Full Text]  
  • Lombardo, E., Ramírez, J. C., Agbandje-McKenna, M., Almendral, J. M. (2000). A Beta-Stranded Motif Drives Capsid Protein Oligomers of the Parvovirus Minute Virus of Mice into the Nucleus for Viral Assembly. J. Virol. 74: 3804-3814 [Abstract] [Full Text]  
  • Lai, M.-C., Lin, R.-I., Huang, S.-Y., Tsai, C.-W., Tarn, W.-Y. (2000). A Human Importin-beta Family Protein, Transportin-SR2, Interacts with the Phosphorylated RS Domain of SR Proteins. J. Biol. Chem. 275: 7950-7957 [Abstract] [Full Text]  
  • Welch, K., Franke, J., Kohler, M., Macara, I. G. (1999). RanBP3 Contains an Unusual Nuclear Localization Signal That Is Imported Preferentially by Importin-alpha 3. Mol. Cell. Biol. 19: 8400-8411 [Abstract] [Full Text]  
  • Hamza, I., Schaefer, M., Klomp, L. W. J., Gitlin, J. D. (1999). Interaction of the copper chaperone HAH1 with the Wilson disease protein is essential for copper homeostasis. Proc. Natl. Acad. Sci. USA 96: 13363-13368 [Abstract] [Full Text]  
  • Morehouse, H., Buratowski, R. M., Silver, P. A., Buratowski, S. (1999). The importin/karyopherin Kap114 mediates the nuclear import of TATA-binding protein. Proc. Natl. Acad. Sci. USA 96: 12542-12547 [Abstract] [Full Text]  
  • Titov, A. A., Blobel, G. (1999). The Karyopherin Kap122p/Pdr6p Imports Both Subunits of the Transcription Factor Iia into the Nucleus. JCB 147: 235-246 [Abstract] [Full Text]  
  • Bear, J., Tan, W., Zolotukhin, A. S., Tabernero, C., Hudson, E. A., Felber, B. K. (1999). Identification of Novel Import and Export Signals of Human TAP, the Protein That Binds to the Constitutive Transport Element of the Type D Retrovirus mRNAs. Mol. Cell. Biol. 19: 6306-6317 [Abstract] [Full Text]  
  • Takizawa, C. G., Weis, K., Morgan, D. O. (1999). Ran-independent nuclear import of cyclin B1-Cdc2 by importin beta. Proc. Natl. Acad. Sci. USA 96: 7938-7943 [Abstract] [Full Text]  
  • Truant, R., Cullen, B. R. (1999). The Arginine-Rich Domains Present in Human Immunodeficiency Virus Type 1 Tat and Rev Function as Direct Importin beta -Dependent Nuclear Localization Signals. Mol. Cell. Biol. 19: 1210-1217 [Abstract] [Full Text]  
  • Xiao, Z., Liu, X., Lodish, H. F. (2000). Importin beta Mediates Nuclear Translocation of Smad 3. J. Biol. Chem. 275: 23425-23428 [Abstract] [Full Text]  
  • Perander, M., Bjorkoy, G., Johansen, T. (2001). Nuclear Import and Export Signals Enable Rapid Nucleocytoplasmic Shuttling of the Atypical Protein Kinase C lambda. J. Biol. Chem. 276: 13015-13024 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»