Unknown

Dataset Information

0

TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death.


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.

SUBMITTER: Ohoka N 

PROVIDER: S-EPMC556400 | biostudies-literature | 2005 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death.

Ohoka Nobumichi N   Yoshii Satoshi S   Hattori Takayuki T   Onozaki Kikuo K   Hayashi Hidetoshi H  

The EMBO journal 20050310 6


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  ...[more]

Similar Datasets

| S-EPMC6258711 | biostudies-literature
| S-EPMC7990929 | biostudies-literature
| S-EPMC6372623 | biostudies-literature
| S-EPMC6991694 | biostudies-literature
| S-EPMC9820715 | biostudies-literature
| S-EPMC6770509 | biostudies-literature
| S-EPMC5669883 | biostudies-literature
| S-EPMC4618488 | biostudies-literature
| S-EPMC2719873 | biostudies-literature
| S-EPMC3006201 | biostudies-literature