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 Black, B. E.
Right arrow Articles by Paschal, B. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Black, B. E.
Right arrow Articles by Paschal, B. M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 1999, p. 8616-8624, Vol. 19, No. 12
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Identification of an NTF2-Related Factor That Binds Ran-GTP and Regulates Nuclear Protein Export

Ben E. Black,1,2,3 Lyne Lévesque,1,2 James M. Holaska,1 Todd C. Wood,2 and Bryce M. Paschal1,2,3,*

Center for Cell Signaling,1 Department of Biochemistry and Molecular Genetics,2 and Cell and Molecular Biology Program,3 University of Virginia Health Sciences Center, Charlottesville, Virginia 22908

Received 14 July 1999/Returned for modification 24 August 1999/Accepted 3 September 1999

Active transport of macromolecules between the nucleus and cytoplasm requires signals for import and export and their recognition by shuttling receptors. Each class of macromolecule is thought to have a distinct receptor that mediates the transport reaction. Assembly and disassembly reactions of receptor-substrate complexes are coordinated by Ran, a GTP-binding protein whose nucleotide state is regulated catalytically by effector proteins. Ran function is modulated in a noncatalytic fashion by NTF2, a protein that mediates nuclear import of Ran-GDP. Here we characterize a novel component of the Ran system that is 26% identical to NTF2, which based on its function we refer to as NTF2-related export protein 1 (NXT1). In contrast to NTF2, NXT1 preferentially binds Ran-GTP, and it colocalizes with the nuclear pore complex (NPC) in mammalian cells. These properties, together with the fact that NXT1 shuttles between the nucleus and the cytoplasm, suggest an active role in nuclear transport. Indeed, NXT1 stimulates nuclear protein export of the NES-containing protein PKI in vitro. The export function of NXT1 is blocked by the addition of leptomycin B, a compound that selectively inhibits the NES receptor Crm1. Thus, NXT1 regulates the Crm1-dependent export pathway through its direct interaction with Ran-GTP.

* Corresponding author. Mailing address: 7161 Hospital West, Box 577 Health Science Center, University of Virginia, Charlottesville, VA 22908. Phone: (804) 243-6521. Fax: (804) 924-1236. E-mail: paschal{at}virginia.edu.

Molecular and Cellular Biology, December 1999, p. 8616-8624, Vol. 19, No. 12
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Kesler, C. T., Gioeli, D., Conaway, M. R., Weber, M. J., Paschal, B. M. (2007). Subcellular Localization Modulates Activation Function 1 Domain Phosphorylation in the Androgen Receptor. Mol. Endocrinol. 21: 2071-2084 [Abstract] [Full Text]  
  • Swartz, J. E., Bor, Y.-C., Misawa, Y., Rekosh, D., Hammarskjold, M.-L. (2007). The Shuttling SR Protein 9G8 Plays a Role in Translation of Unspliced mRNA Containing a Constitutive Transport Element. J. Biol. Chem. 282: 19844-19853 [Abstract] [Full Text]  
  • Bogerd, H. P., Wiegand, H. L., Hulme, A. E., Garcia-Perez, J. L., O'Shea, K. S., Moran, J. V., Cullen, B. R. (2006). Cellular inhibitors of long interspersed element 1 and Alu retrotransposition. Proc. Natl. Acad. Sci. USA 103: 8780-8785 [Abstract] [Full Text]  
  • Levesque, L., Bor, Y.-C., Matzat, L. H., Jin, L., Berberoglu, S., Rekosh, D., Hammarskjold, M.-L., Paschal, B. M. (2006). Mutations in Tap Uncouple RNA Export Activity from Translocation through the Nuclear Pore Complex. Mol. Biol. Cell 17: 931-943 [Abstract] [Full Text]  
  • de Oca, R. M., Lee, K. K., Wilson, K. L. (2005). Binding of Barrier to Autointegration Factor (BAF) to Histone H3 and Selected Linker Histones Including H1.1. J. Biol. Chem. 280: 42252-42262 [Abstract] [Full Text]  
  • Kendirgi, F., Rexer, D. J., Alcazar-Roman, A. R., Onishko, H. M., Wente, S. R. (2005). Interaction between the Shuttling mRNA Export Factor Gle1 and the Nucleoporin hCG1: A Conserved Mechanism in the Export of Hsp70 mRNA. Mol. Biol. Cell 16: 4304-4315 [Abstract] [Full Text]  
  • Chen, T., Brownawell, A. M., Macara, I. G. (2004). Nucleocytoplasmic Shuttling of JAZ, a New Cargo Protein for Exportin-5. Mol. Cell. Biol. 24: 6608-6619 [Abstract] [Full Text]  
  • Thakurta, A. G., Gopal, G., Yoon, J. H., Saha, T., Dhar, R. (2004). Conserved Nuclear Export Sequences in Schizosaccharomyces pombe Mex67 and Human TAP Function in mRNA Export by Direct Nuclear Pore Interactions. J. Biol. Chem. 279: 17434-17442 [Abstract] [Full Text]  
  • Jin, L., Guzik, B. W., Bor, Y.-c., Rekosh, D., Hammarskjold, M.-L. (2003). Tap and NXT promote translation of unspliced mRNA. Genes Dev. 17: 3075-3086 [Abstract] [Full Text]  
  • Holaska, J. M., Lee, K. K., Kowalski, A. K., Wilson, K. L. (2003). Transcriptional Repressor Germ Cell-less (GCL) and Barrier to Autointegration Factor (BAF) Compete for Binding to Emerin in Vitro. J. Biol. Chem. 278: 6969-6975 [Abstract] [Full Text]  
  • Siebrasse, J. P., Coutavas, E., Peters, R. (2002). Reconstitution of nuclear protein export in isolated nuclear envelopes. JCB 158: 849-854 [Abstract] [Full Text]  
  • Holaska, J. M., Black, B. E., Rastinejad, F., Paschal, B. M. (2002). Ca2+-Dependent Nuclear Export Mediated by Calreticulin. Mol. Cell. Biol. 22: 6286-6297 [Abstract] [Full Text]  
  • Braun, I. C., Herold, A., Rode, M., Izaurralde, E. (2002). Nuclear Export of mRNA by TAP/NXF1 Requires Two Nucleoporin-Binding Sites but Not p15. Mol. Cell. Biol. 22: 5405-5418 [Abstract] [Full Text]  
  • Kunzler, M., Hurt, E. (2002). Targeting of Ran: variation on a common theme?. J. Cell Sci. 114: 3233-3241 [Abstract] [Full Text]  
  • Lorkovic, Z. J., Barta, A. (2002). Genome analysis: RNA recognition motif (RRM) and K homology (KH) domain RNA-binding proteins from the flowering plant Arabidopsis thaliana. Nucleic Acids Res 30: 623-635 [Abstract] [Full Text]  
  • Wiegand, H. L., Coburn, G. A., Zeng, Y., Kang, Y., Bogerd, H. P., Cullen, B. R. (2002). Formation of Tap/NXT1 Heterodimers Activates Tap-Dependent Nuclear mRNA Export by Enhancing Recruitment to Nuclear Pore Complexes. Mol. Cell. Biol. 22: 245-256 [Abstract] [Full Text]  
  • Macara, I. G. (2001). Transport into and out of the Nucleus. Microbiol. Mol. Biol. Rev. 65: 570-594 [Abstract] [Full Text]  
  • Schmitt, I., Gerace, L. (2001). In Vitro Analysis of Nuclear Transport Mediated by the C-terminal Shuttle Domain of Tap. J. Biol. Chem. 276: 42355-42363 [Abstract] [Full Text]  
  • Lindsay, M. E., Holaska, J. M., Welch, K., Paschal, B. M., Macara, I. G. (2001). Ran-Binding Protein 3 Is a Cofactor for Crm1-Mediated Nuclear Protein Export. JCB 153: 1391-1402 [Abstract] [Full Text]  
  • Brownawell, A. M., Kops, G. J. P. L., Macara, I. G., Burgering, B. M. T. (2001). Inhibition of Nuclear Import by Protein Kinase B (Akt) Regulates the Subcellular Distribution and Activity of the Forkhead Transcription Factor AFX. Mol. Cell. Biol. 21: 3534-3546 [Abstract] [Full Text]  
  • Guzik, B. W., Levesque, L., Prasad, S., Bor, Y.-C., Black, B. E., Paschal, B. M., Rekosh, D., Hammarskjöld, M.-L. (2001). NXT1 (p15) Is a Crucial Cellular Cofactor in TAP-Dependent Export of Intron-Containing RNA in Mammalian Cells. Mol. Cell. Biol. 21: 2545-2554 [Abstract] [Full Text]  
  • Holaska, J. M., Black, B. E., Love, D. C., Hanover, J. A., Leszyk, J., Paschal, B. M. (2001). Calreticulin Is a Receptor for Nuclear Export. JCB 152: 127-140 [Abstract] [Full Text]  
  • Black, B. E., Holaska, J. M., Levesque, L., Ossareh-Nazari, B., Gwizdek, C., Dargemont, C., Paschal, B. M. (2001). Nxt1 Is Necessary for the Terminal Step of Crm1-Mediated Nuclear Export. JCB 152: 141-156 [Abstract] [Full Text]  
  • Yoon, J. H., Love, D. C., Guhathakurta, A., Hanover, J. A., Dhar, R. (2000). Mex67p of Schizosaccharomyces pombe Interacts with Rae1p in Mediating mRNA Export. Mol. Cell. Biol. 20: 8767-8782 [Abstract] [Full Text]  
  • Herold, A., Suyama, M., Rodrigues, J. P., Braun, I. C., Kutay, U., Carmo-Fonseca, M., Bork, P., Izaurralde, E. (2000). TAP (NXF1) Belongs to a Multigene Family of Putative RNA Export Factors with a Conserved Modular Architecture. Mol. Cell. Biol. 20: 8996-9008 [Abstract] [Full Text]  
  • Lane, C. M., Cushman, I., Moore, M. S. (2000). Selective Disruption of Nuclear Import by a Functional Mutant Nuclear Transport Carrier. JCB 151: 321-332 [Abstract] [Full Text]  
  • Ossareh-Nazari, B., Maison, C., Black, B. E., Lévesque, L., Paschal, B. M., Dargemont, C. (2000). RanGTP-Binding Protein NXT1 Facilitates Nuclear Export of Different Classes of RNA In Vitro. Mol. Cell. Biol. 20: 4562-4571 [Abstract] [Full Text]  
  • Steggerda, S. M., Black, B. E., Paschal, B. M. (2000). Monoclonal Antibodies to NTF2 Inhibit Nuclear Protein Import by Preventing Nuclear Translocation of the GTPase Ran. Mol. Biol. Cell 11: 703-719 [Abstract] [Full Text]  
  • Steggerda, S. M., Paschal, B. M. (2000). The Mammalian Mog1 Protein Is a Guanine Nucleotide Release Factor for Ran. J. Biol. Chem. 275: 23175-23180 [Abstract] [Full Text]  
  • Braun, I. C., Herold, A., Rode, M., Conti, E., Izaurralde, E. (2001). Overexpression of TAP/p15 Heterodimers Bypasses Nuclear Retention and Stimulates Nuclear mRNA Export. J. Biol. Chem. 276: 20536-20543 [Abstract] [Full Text]  
  • Levesque, L., Guzik, B., Guan, T., Coyle, J., Black, B. E., Rekosh, D., Hammarskjold, M.-L., Paschal, B. M. (2001). RNA Export Mediated by Tap Involves NXT1-dependent Interactions with the Nuclear Pore Complex. J. Biol. Chem. 276: 44953-44962 [Abstract] [Full Text]  
  • Brownawell, A. M., Macara, I. G. (2002). Exportin-5, a novel karyopherin, mediates nuclear export of double-stranded RNA binding proteins. JCB 156: 53-64 [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»