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| Content Provider | PubMed Central |
|---|---|
| Author | Ohoka, Nobumichi Yoshii, Satoshi Hattori, Takayuki Onozaki, Kikuo Hayashi, Hidetoshi |
| Copyright Year | 2005 |
| Abstract | C/EBP homologous protein (CHOP) is a stress-inducible nuclear protein that is crucial for the development of programmed cell death and regeneration; however, the regulation of its function has not been well characterized. Slbo, a Drosophila homolog of C/EBP (CCAAT/enhancer binding protein), was shown to be unstabilized by tribbles. Here, we identified TRB3 as a tribbles ortholog in humans, which associated with CHOP to suppress the CHOP-dependent transactivation. TRB3 is induced by various forms endoplasmic reticulum (ER) stress later than CHOP. Tunicamycin treatment enhanced the TRB3 promoter activity, while dominant-negative forms of CHOP suppressed the tunicamycin-induced activation. In addition, the tunicamycin response region in the TRB3 promoter contains amino-acid response elements overlapping the CHOP-binding site, and CHOP and ATF4 cooperated to activate this promoter activity. Knockdown of endogenous ATF4 or CHOP expression dramatically repressed tunicamycin-induced TRB3 induction. Furthermore, knockdown of TRB3 expression decreased ER stress-dependent cell death. These results indicate that TRB3 is a novel target of CHOP/ATF4 and downregulates its own induction by repression of CHOP/ATF4 functions, and that it is involved in CHOP-dependent cell death during ER stress. |
| Related Links | http://dx.doi.org/10.1038/sj.emboj.7600596 |
| Ending Page | 1255 |
| Page Count | 13 |
| Starting Page | 1243 |
| File Format | |
| ISSN | 02614189 |
| e-ISSN | 14602075 |
| Journal | The EMBO Journal |
| Issue Number | 6 |
| Volume Number | 24 |
| Language | English |
| Publisher Date | 2005-03-01 |
| Access Restriction | Open |
| Subject Keyword | Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Neuroscience(all) Molecular Biology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Immunology and Microbiology Medicine Molecular Biology |
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