| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print July 31, 2003
Laboratoire Jacques Ghysdael - CNRS UMR146, Institut Curie, Orsay, Ile de France 91405
Corresponding Author: Rodolphe.Lopez{at}EMBL-Monterotondo.it
TEL is a frequent target of chromosomal translocations in human cancer and an alledged tumor suppressor gene. TEL encodes two isoforms: a major TEL-M1 isoform as well as TEL-M43, which lacks the first 42 amino-acid residues of TEL-M1. Both isoforms are po tent transcriptional repressors that can inhibit RAS-induced transformation. Here we show that the v-SRC protein tyrosine kinase relieves the repressive activity of TEL-M1, an activity which is associated with the v-SRC-induced delocalization of TEL-M1 fr om the nucleus to the cytoplasm. TEL-M1 delocalization requires the kinase activity of v-SRC and is not induced by oncogenic RAS or AKT. Cytoplasmic delocalization of TEL-M1 in response to v-SRC critically depends upon its unique amino-terminal domain (SRCD domain) since (i) v-SRC did not inhibit the repressive properties of TEL-M43, nor affected TEL-M43 nuclear localization; (ii) fusion of the first 52 amino-acid residues of TEL-M1 to FLI-1, an ETS protein insensitive to v-SRC-induced delocalization, i s sufficient to confer v-SRC-induced delocalization to this TEL/FLI-1 chimeric protein. The v-SRC-induced nucleocytoplasmic delocalization of TEL-M1 does not involve phosphorylation of the SRCD and does not require TEL self-association and repressive doma in s. Finally, enforced expression of the v-SRC-insensitive TEL-M43 - but not of TEL-M1 - inhibits v-SRC-induced transformation of NIH3T3 fibroblasts. These results identify a regulatory domain in TEL which specifically impinges on the subcellular localiz ati on of its major TEL-M1 isoform. They furthermore indicate that inhibition of TEL-M1 nuclear function is required in order for v-SRC to induce cellular transformation. o
J. Biol. Chem, 10.1074/jbc.M306435200
Submitted on June 18, 2003
Revised on July 30, 2003
Accepted on July 31, 2003
V-SRC specifically regulates the nucleo-cytoplasmic delocalisation of the major isoform of TEL (ETV6)
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. G. Roukens, M. Alloul-Ramdhani, A. C. O. Vertegaal, Z. Anvarian, C. I. A. Balog, A. M. Deelder, P. J. Hensbergen, and D. A. Baker Identification of a New Site of Sumoylation on Tel (ETV6) Uncovers a PIAS-Dependent Mode of Regulating Tel Function Mol. Cell. Biol., April 1, 2008; 28(7): 2342 - 2357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Niu, F. Roy, F. Saltel, C. Andrieu-Soler, W. Dong, A.-L. Chantegrel, R. Accardi, A. Thepot, N. Foiselle, M. Tommasino, et al. A nuclear export signal and phosphorylation regulate dok1 subcellular localization and functions. Mol. Cell. Biol., June 1, 2006; 26(11): 4288 - 4301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Prescott, K. S. N. Koto, M. Singh, and A. Gutierrez-Hartmann The ETS Transcription Factor ESE-1 Transforms MCF-12A Human Mammary Epithelial Cells via a Novel Cytoplasmic Mechanism Mol. Cell. Biol., June 15, 2004; 24(12): 5548 - 5564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Galang, W. J. Muller, G. Foos, R. G. Oshima, and C. A. Hauser Changes in the Expression of Many Ets Family Transcription Factors and of Potential Target Genes in Normal Mammary Tissue and Tumors J. Biol. Chem., March 19, 2004; 279(12): 11281 - 11292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Frame Newest findings on the oldest oncogene; how activated src does it J. Cell Sci., March 1, 2004; 117(7): 989 - 998. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
