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Novel interaction between the transcription factor CHOP (GADD153) and the ribosomal protein FTE/S3a modulates erythropoiesis

Item Type:Article
Title:Novel interaction between the transcription factor CHOP (GADD153) and the ribosomal protein FTE/S3a modulates erythropoiesis
Creators Name:Cui, K.Y. and Coutts, M. and Stahl, J. and Sytkowski, A.J.
Abstract:The transcription factor CHOP (GADD153) heterodimerizes with other C/EBP family members, especially C/EBPβ, thus preventing their homodimerization and binding to DNA sequences specific for the homodimers. Some CHOP-C/EBP heterodimers apparently bind to alternative DNA sequence and thereby regulate the transcription of other genes. Recently, we demonstrated that CHOP is up- regulated during certain stages of erythroid differentiation and that ectopic overexpression of CHOP enhances this process (Coutts, M., Cui, K., Davis, K. L., Keutzer, J. C., and Sytkowski, A. J. (1999) Blood 93, 3369-3378). In the present study, we report that CHOP also interacts with another non-C/EBP protein designated v-fos transformation effector (FTE) (Kho, C. J., and Zarbl, H. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 2200-2204), which is identical to ribosomal protein S3a (Metspalu, A., Rebane, A., Hoth, S,, Pooga, M., Stahl, J., and Kruppa, J. (1992) Gene (Amst.) 119, 313-316). Bacterially expressed His-CHOP and in vitro translated 35S-labeled FTE/S3a- Ga14 fusion protein co-immunoprecipitated using anti-CHOP antibodies, and both anti-CHOP and anti-FTE/S3a antibodies co-immunoprecipitated CHOP and FTE/S3a from lysates of Rauscher murine erythroleukemia cells overexpressing both proteins. The in vivo interaction of CHOP and FTE/S3a was also demonstrated in cells overexpressing FTE/S3a but with endogenous expression levels of CHOP. Western blot analysis demonstrated co-localization of CHOP and FTE/S3a in both the cytosol and the nuclei of non-transfected cells. Overexpression of FTE/S3a inhibited differentiation of Rauscher cells induced either by erythropoietin or by dimethyl sulfoxide. This inhibition was reversed partially by simultaneous overexpression of CHOP or of antisense fte/S3a. FTE/S3a appears to be a bifunctional ribosomal protein that regulates CHOP and, hence, C/EBP function during erythropoiesis.
Keywords:Antisense Elements (Genetics), CCAAT-Enhancer-Binding Proteins, Cell Compartmentation, Cell Differentiation, Cell Nucleus, Cytoplasm, DNA-Binding Proteins, Erythroid Progenitor Cells, Erythropoiesis, Nuclear Proteins, Protein Binding, Recombinant Proteins, Ribosomal Proteins, Transcription Factor CHOP, Transcription Factors, Two-Hybrid System Techniques, Animals, Mice
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:275
Number:11
Page Range:7591-7596
Date:17 March 2000
Official Publication:http://www.jbc.org/cgi/content/abstract/275/11/7591
PubMed:View item in PubMed

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