Topic
TRIB3
About: TRIB3 is a research topic. Over the lifetime, 129 publications have been published within this topic receiving 7048 citations. The topic is also known as: C20orf97 & NIPK.
Papers published on a yearly basis
Papers
TL;DR: The 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.
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.
1,009 citations
TL;DR: It is shown that TRB3, a mammalian homolog of Drosophila tribbles, functions as a negative modulator of Akt, which contributes to insulin resistance in individuals with susceptibility to type II diabetes.
Abstract: Insulin resistance is a major hallmark in the development of type II diabetes, which is characterized by the failure of insulin to promote glucose uptake in muscle and to suppress glucose production in liver. The serine-threonine kinase Akt (PKB) is a principal target of insulin signaling that inhibits hepatic glucose output when glucose is available from food. Here we show that TRB3, a mammalian homolog of Drosophila tribbles, functions as a negative modulator of Akt. TRB3 expression is induced in liver under fasting conditions, and TRB3 disrupts insulin signaling by binding directly to Akt and blocking activation of the kinase. Amounts of TRB3 RNA and protein were increased in livers of db/db diabetic mice compared with those in wild-type mice. Hepatic overexpression of TRB3 in amounts comparable to those in db/db mice promoted hyperglycemia and glucose intolerance. Our results suggest that, by interfering with Akt activation, TRB3 contributes to insulin resistance in individuals with susceptibility to type II diabetes.
881 citations
TL;DR: By regulating CDC25, Tribbles serves to coordinate entry into mitosis with morphogenesis and cell fate determination, and acts by specifically inducing degradation of the CDC25 mitotic activators String and Twine via the proteosome pathway.
373 citations
TL;DR: Because transgenic mice expressing TRB3 in adipose tissue are protected from diet-induced obesity due to enhanced fatty acid oxidation, these results demonstrate how phosphorylation and ubiquitination pathways converge on a key regulator of lipid metabolism to maintain energy homeostasis.
Abstract: During fasting, increased concentrations of circulating catecholamines promote the mobilization of lipid stores from adipose tissue in part by phosphorylating and inactivating acetyl-coenzyme A carboxylase (ACC), the rate-limiting enzyme in fatty acid synthesis. Here, we describe a parallel pathway, in which the pseudokinase Tribbles 3 (TRB3), whose abundance is increased during fasting, stimulates lipolysis by triggering the degradation of ACC in adipose tissue. TRB3 promoted ACC ubiquitination through an association with the E3 ubiquitin ligase constitutive photomorphogenic protein 1 (COP1). Indeed, adipocytes deficient in TRB3 accumulated larger amounts of ACC protein than did wild-type cells. Because transgenic mice expressing TRB3 in adipose tissue are protected from diet-induced obesity due to enhanced fatty acid oxidation, these results demonstrate how phosphorylation and ubiquitination pathways converge on a key regulator of lipid metabolism to maintain energy homeostasis.
320 citations
TL;DR: It is shown that it is essential that mitosis be blocked in the mesoderm during early gastrulation, and identified the putative serine/threonine kinase Tribbles as controlling this block.
265 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 19 |
| 2020 | 8 |
| 2019 | 8 |
| 2018 | 5 |
| 2017 | 13 |
| 2016 | 8 |