1. Phosphorylation regulates the subcellular location and activity of the snail transcriptional repressor
- Author
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Bàrbara Montserrat-Sentís, Judit Grueso, Isabel Puig, Josep Baulida, Ariadna Virgós-Soler, David Domı́nguez, Clara Francí, Sandra Guaita, Antonio García de Herreros, and Montserrat Porta
- Subjects
Molecular Sequence Data ,Nuclear Localization Signals ,Active Transport, Cell Nucleus ,Receptors, Cytoplasmic and Nuclear ,Snail ,Biology ,Karyopherins ,Gene product ,Mice ,Cytosol ,Leucine ,biology.animal ,parasitic diseases ,Extracellular ,Serine ,Tumor Cells, Cultured ,Animals ,Humans ,Phosphorylation ,Nuclear export signal ,Molecular Biology ,Zinc finger ,Cell Nucleus ,Transcriptional Regulation ,Base Sequence ,fungi ,Cell Biology ,Molecular biology ,Cell biology ,Extracellular Matrix ,Protein Structure, Tertiary ,DNA-Binding Proteins ,Repressor Proteins ,Protein Transport ,Snail Family Transcription Factors ,Intracellular ,Subcellular Fractions ,Transcription Factors - Abstract
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.
- Published
- 2003