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

被引:45
作者
Cui, KY
Coutts, M
Stahl, J
Sytkowski, AJ [1 ]
机构
[1] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Lab Cell & Mol Biol, Boston, MA 02215 USA
[2] Max Delbruck Ctr Mol Med, D-13122 Berlin, Germany
关键词
D O I
10.1074/jbc.275.11.7591
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The transcription factor CHOP (GADD153) heterodimerizes with other C/EBP family members, especially CIEBP beta, 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, NI., Stahl, J., and Kruppa, J. (1992) Gene (Amst.) 119, 313-316). Bacterially expressed His-CHOP and in vitro translated S-35-labeled FTE/S3a-Gal4 fusion protein coimmunoprecipitated 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 nontransfected 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.
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页码:7591 / 7596
页数:6
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