SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on August 28, 2003; DOI 10.1182/blood-2003-06-2077. This Article Full Text (PDF) All Versions of this Article: 2003-06-2077v1 102/13/4555    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lebigot, I. Articles by Tran Quang, C. Search for Related Content PubMed PubMed Citation Articles by Lebigot, I. Articles by Tran Quang, C. Social Bookmarking                   What's this? Submitted June 25, 2003 Accepted August 14, 2003 Up-regulation of SLAP in FLI-1-transformed erythroblasts interferes with EpoR signaling Ingrid Lebigot, Paola Gardellin, Laurent Lefebvre, Hartmut Beug, Jacques Ghysdael, and Christine Tran Quang* UMR 146 du CNRS, Institut Curie, Orsay, France Institute of Molecular Pathology, Vienna, Austria * Corresponding author; email: Christine.Tran-Quang{at}curie.u-psud.fr. Rearrangement of the FLI-1 locus and ensuing overexpression of FLI-1 protein is an early event in F-MLV-induced erythroleukemia. When overexpressed in primary erythroblasts, FLI-1 converts Epo-induced terminal differentiation into a proliferative response. We found that SLAP, a gene encoding a recently described negative regulator of T cell antigen receptor function during thymocyte development, is up-regulated both at the RNA and protein levels in FLI-1-transformed erythroblasts. SLAP was found in a specific complex with EpoR, a cytokine receptor essential to erythroid differentiation. Constitutive expression of SLAP severely impairs hemoglobinization and late survival during Epo-induced terminal differentiation of erythroblasts. This is associated with the specific inhibition of several critical Epo-dependent signaling events including STAT5 activation and upregulation of the expression of the anti-apoptotic BCL-X gene. Our data support a model by which FLI-1 inhibits normal erythroid differentiation through the deregulation of genes encoding adaptors/effectors that modify the signaling output of cytokine receptors normally required for terminal differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Juban, G. Giraud, B. Guyot, S. Belin, J.-J. Diaz, J. Starck, C. Guillouf, F. Moreau-Gachelin, and F. Morle Spi-1 and Fli-1 Directly Activate Common Target Genes Involved in Ribosome Biogenesis in Friend Erythroleukemic Cells Mol. Cell. Biol., May 15, 2009; 29(10): 2852 - 2864. [Abstract] [Full Text] [PDF] B. Pakuts, C. Debonneville, L. M. Liontos, M. P. Loreto, and C. J. McGlade The Src-like Adaptor Protein 2 Regulates Colony-stimulating Factor-1 Receptor Signaling and Down-regulation J. Biol. Chem., June 22, 2007; 282(25): 17953 - 17963. [Abstract] [Full Text] [PDF] E. van den Akker, S. Ano, H.-M. Shih, L.-C. Wang, M. Pironin, J. J. Palvimo, N. Kotaja, O. Kirsh, A. Dejean, and J. Ghysdael FLI-1 Functionally Interacts with PIASx{alpha}, a Member of the PIAS E3 SUMO Ligase Family J. Biol. Chem., November 11, 2005; 280(45): 38035 - 38046. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020