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 Domínguez, D.
Right arrow Articles by García de Herreros, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Domínguez, D.
Right arrow Articles by García de Herreros, A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2003, p. 5078-5089, Vol. 23, No. 14
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.14.5078-5089.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Phosphorylation Regulates the Subcellular Location and Activity of the Snail Transcriptional Repressor

David Domínguez, Bàrbara Montserrat-Sentís, Ariadna Virgós-Soler, Sandra Guaita, Judit Grueso, Montserrat Porta, Isabel Puig, Josep Baulida, Clara Francí, and Antonio García de Herreros*

Unitat de Biologia Cel·lular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, 08003 Barcelona, Spain

Received 30 December 2002/ Returned for modification 3 February 2003/ Accepted 1 May 2003

The Snail gene product is a transcriptional repressor of E-cadherin expression and an inducer of the epithelial-to-mesenchymal transition in several epithelial tumor cell lines. This report presents data indicating that Snail function is controlled by its intracellular location. The cytosolic distribution of Snail depended on export from the nucleus by a CRM1-dependent mechanism, and a nuclear export sequence (NES) was located in the regulatory domain of this protein. Export of Snail was controlled by phosphorylation of a Ser-rich sequence adjacent to this NES. Modification of this sequence released the restriction created by the zinc finger domain and allowed nuclear export of the protein. The phosphorylation and subcellular distribution of Snail are controlled by cell attachment to the extracellular matrix. Suspended cells presented higher levels of phosphorylated Snail and an augmented extranuclear localization with respect to cells attached to the plate. These findings show the existence in tumor cells of an effective and fine-tuning nontranscriptional mechanism of regulation of Snail activity dependent on the extracellular environment.

* Corresponding author. Mailing address: Unitat de Biologia Cel·lular i Molecular, Institut Municipal d'Investigació Mèdica, c/Doctor Aiguader 80, 08003 Barcelona, Spain. Phone: 34-93-221 1009. Fax: 34-93-221 3237. E-mail: agarcia{at}imim.es.

Molecular and Cellular Biology, July 2003, p. 5078-5089, Vol. 23, No. 14
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.14.5078-5089.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Maures, T. J., Chen, L., Carter-Su, C. (2009). Nucleocytoplasmic Shuttling of the Adapter Protein SH2B1{beta} (SH2-B{beta}) Is Required for Nerve Growth Factor (NGF)-Dependent Neurite Outgrowth and Enhancement of Expression of a Subset of NGF-Responsive Genes. Mol. Endocrinol. 23: 1077-1091 [Abstract] [Full Text]  
  • Mingot, J.-M., Vega, S., Maestro, B., Sanz, J. M., Nieto, M. A. (2009). Characterization of Snail nuclear import pathways as representatives of C2H2 zinc finger transcription factors. J. Cell Sci. 122: 1452-1460 [Abstract] [Full Text]  
  • Smith, J. P., Pozzi, A., Dhawan, P., Singh, A. B., Harris, R. C. (2009). Soluble HB-EGF induces epithelial-to-mesenchymal transition in inner medullary collecting duct cells by upregulating Snail-2. Am. J. Physiol. Renal Physiol. 296: F957-F965 [Abstract] [Full Text]  
  • Fedorova, L. V., Raju, V., El-Okdi, N., Shidyak, A., Kennedy, D. J., Vetteth, S., Giovannucci, D. R., Bagrov, A. Y., Fedorova, O. V., Shapiro, J. I., Malhotra, D. (2009). The cardiotonic steroid hormone marinobufagenin induces renal fibrosis: implication of epithelial-to-mesenchymal transition. Am. J. Physiol. Renal Physiol. 296: F922-F934 [Abstract] [Full Text]  
  • Pon, Y. L., Zhou, H. Y., Cheung, A. N.Y., Ngan, H. Y.S., Wong, A. S.T. (2008). p70 S6 Kinase Promotes Epithelial to Mesenchymal Transition through Snail Induction in Ovarian Cancer Cells. Cancer Res. 68: 6524-6532 [Abstract] [Full Text]  
  • Solanas, G., Porta-de-la-Riva, M., Agusti, C., Casagolda, D., Sanchez-Aguilera, F., Larriba, M. J., Pons, F., Peiro, S., Escriva, M., Munoz, A., Dunach, M., de Herreros, A. G., Baulida, J. (2008). E-cadherin controls {beta}-catenin and NF-{kappa}B transcriptional activity in mesenchymal gene expression. J. Cell Sci. 121: 2224-2234 [Abstract] [Full Text]  
  • Escriva, M., Peiro, S., Herranz, N., Villagrasa, P., Dave, N., Montserrat-Sentis, B., Murray, S. A., Franci, C., Gridley, T., Virtanen, I., Garcia de Herreros, A. (2008). Repression of PTEN Phosphatase by Snail1 Transcriptional Factor during Gamma Radiation-Induced Apoptosis. Mol. Cell. Biol. 28: 1528-1540 [Abstract] [Full Text]  
  • Bernreiter, A., Ramon, A., Fernandez-Martinez, J., Berger, H., Araujo-Bazan, L., Espeso, E. A., Pachlinger, R., Gallmetzer, A., Anderl, I., Scazzocchio, C., Strauss, J. (2007). Nuclear Export of the Transcription Factor NirA Is a Regulatory Checkpoint for Nitrate Induction in Aspergillus nidulans. Mol. Cell. Biol. 27: 791-802 [Abstract] [Full Text]  
  • Takkunen, M., Grenman, R., Hukkanen, M., Korhonen, M., Garcia de Herreros, A., Virtanen, I. (2006). Snail-dependent and -independent Epithelial-Mesenchymal Transition in Oral Squamous Carcinoma Cells. J. Histochem. Cytochem. 54: 1263-1275 [Abstract] [Full Text]  
  • Vernon, A. E., LaBonne, C. (2006). Slug stability is dynamically regulated during neural crest development by the F-box protein Ppa. Development 133: 3359-3370 [Abstract] [Full Text]  
  • Lee, J. M., Dedhar, S., Kalluri, R., Thompson, E. W. (2006). The epithelial-mesenchymal transition: new insights in signaling, development, and disease.. JCB 172: 973-981 [Abstract] [Full Text]  
  • Raurell, I., Castano, J., Franci, C., de Herreros, A. G., Dunach, M. (2006). Presenilin-1 Interacts with Plakoglobin and Enhances Plakoglobin-Tcf-4 Association: IMPLICATIONS FOR THE REGULATION OF beta-CATENIN/Tcf-4-DEPENDENT TRANSCRIPTION. J. Biol. Chem. 281: 1401-1411 [Abstract] [Full Text]  
  • Peiro, S., Escriva, M., Puig, I., Barbera, M. J., Dave, N., Herranz, N., Larriba, M. J., Takkunen, M., Franci, C., Munoz, A., Virtanen, I., Baulida, J., de Herreros, A. G. (2006). Snail1 transcriptional repressor binds to its own promoter and controls its expression.. Nucleic Acids Res 34: 2077-2084 [Abstract] [Full Text]  
  • Rosano, L., Spinella, F., Di Castro, V., Nicotra, M. R., Dedhar, S., de Herreros, A. G., Natali, P. G., Bagnato, A. (2005). Endothelin-1 Promotes Epithelial-to-Mesenchymal Transition in Human Ovarian Cancer Cells. Cancer Res. 65: 11649-11657 [Abstract] [Full Text]  
  • Baranek, C., Sock, E., Wegner, M. (2005). The POU protein Oct-6 is a nucleocytoplasmic shuttling protein. Nucleic Acids Res 33: 6277-6286 [Abstract] [Full Text]  
  • Barrallo-Gimeno, A., Nieto, M. A. (2005). The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development 132: 3151-3161 [Abstract] [Full Text]  
  • Yamasaki, H., Sekimoto, T., Ohkubo, T., Douchi, T., Nagata, Y., Ozawa, M., Yoneda, Y. (2005). Zinc finger domain of Snail functions as a nuclear localization signal for importin {beta}-mediated nuclear import pathway. GENES CELLS 10: 455-464 [Abstract] [Full Text]  
  • Yang, Z., Rayala, S., Nguyen, D., Vadlamudi, R. K., Chen, S., Kumar, R. (2005). Pak1 Phosphorylation of Snail, a Master Regulator of Epithelial-to-Mesenchyme Transition, Modulates Snail's Subcellular Localization and Functions. Cancer Res. 65: 3179-3184 [Abstract] [Full Text]  
  • Yook, J. I., Li, X.-Y., Ota, I., Fearon, E. R., Weiss, S. J. (2005). Wnt-dependent Regulation of the E-cadherin Repressor Snail. J. Biol. Chem. 280: 11740-11748 [Abstract] [Full Text]  
  • Bachelder, R. E., Yoon, S.-O., Franci, C., de Herreros, A. G., Mercurio, A. M. (2005). Glycogen synthase kinase-3 is an endogenous inhibitor of Snail transcription: implications for the epithelial-mesenchymal transition. JCB 168: 29-33 [Abstract] [Full Text]  
  • Mishra, S. K., Talukder, A. H., Gururaj, A. E., Yang, Z., Singh, R. R., Mahoney, M. G., Franci, C., Vadlamudi, R. K., Kumar, R. (2004). Upstream Determinants of Estrogen Receptor-{alpha} Regulation of Metastatic Tumor Antigen 3 Pathway. J. Biol. Chem. 279: 32709-32715 [Abstract] [Full Text]  
  • Song, J. J., Lee, Y. J. (2004). Tryptophan 621 and Serine 667 Residues of Daxx Regulate Its Nuclear Export during Glucose Deprivation. J. Biol. Chem. 279: 30573-30578 [Abstract] [Full Text]  
  • Takenaka, Y., Fukumori, T., Yoshii, T., Oka, N., Inohara, H., Kim, H.-R. C., Bresalier, R. S., Raz, A. (2004). Nuclear Export of Phosphorylated Galectin-3 Regulates Its Antiapoptotic Activity in Response to Chemotherapeutic Drugs. Mol. Cell. Biol. 24: 4395-4406 [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»