Recombinant Mouse Tribbles homolog 3 (Trib3)

1. Using SNRK transgenic and KO mouse models, study found that SNRK decreases cardiac metabolic substrate usage and mitochondrial coupling, while protecting against ischaemia/reperfusion injury. Effects on substrate usage and cell death are dependent on UCP3, which is downregulated through suppression of PPARalpha by Trib3, a novel binding partner of SNRK. PMID: 28117339
2. Overexpressed Trib3, specifically in skeletal muscle tissues, displayed impaired glucose homeostasis by suppressing insulin-stimulated glucose uptake. PMID: 30071535
3. under nutrient-limiting conditions that stimulate ATF4 activity, TRIB3 is implicated in the regulation of metabolic adaptation by restraining the transcription of Fgf21. PMID: 29378327
4. Data (including data from studies in transgenic and mutant mice) suggest that Akt2 plays critical role in type 1 diabetes in metallothionein-mediated preservation of cardiac insulin-stimulated metabolic signaling (insulin resistance) and preservation of cardiac function; this mechanism appear to involve inhibition of cardiac Trb3. (Akt2 = protein kinase Akt-2; Trb3 = tribbles pseudokinase 3) PMID: 29079702
5. restoration of TRB3 expression markedly abolished the effect of miR-124 on hepatic TG metabolism. PMID: 27845424
6. TRIB3, a single-domain protein with impaired kinase catalytic activity, has been described to perform a complex of roles, many of which are likely to be cell type-specific. (Review) PMID: 28393700
7. TRB3 regulates protein synthesis and breakdown via the Akt/mTOR/FoxO pathways in skeletal muscle. PMID: 28962861
8. Under physiological conditions, muscle TRIB3 also influences energy expenditure and substrate metabolism, indicating that the decrease and increase in muscle TRIB3 under fasting and nutrient excess, respectively, are critical for metabolic homeostasis. PMID: 27207527
9. In a knockout mouse model, Trib3 disruption modestly increased steady-state erythrocyte numbers and decreased mean corpuscular volume. PMID: 28062363
10. These data demonstrate that TRB3 inhibits insulin signaling in BAT, resulting in impaired differentiation and function. PMID: 26801556
11. TRB3 is a novel profibrotic mediator in SSc. TGF-beta induces TRB3, which in turn activates canonical TGF-beta/Smad signaling and stimulates the release of collagen, creating a positive feedback loop that may contribute to aberrant TGF-beta signalling in SSc. PMID: 25603829
12. study presents the finding that activation of the NF-kappaB pathway by Porphyromonas endodontalis LPS is important for Wnt5a expression in osteoblasts, and that TRIB3 may modulate the sustained expression of Wnt5a in osteoblasts stimulated by P. endodontalis PMID: 25601649
13. Trib3 interferes with the Parkinson's disease-associated prosurvival protein Parkin to mediate death PMID: 26224857
14. These observations support the notion that loss of TRIB3 is associated with a more aggressive phenotype in various types of tumors by enhancing the activity of the mTORC2/AKT/FOXO axis. PMID: 25168244
15. Tribbles 3 regulates the fibrosis cytokine TGF- beta 1 through ERK1/2-MAPK signaling pathway in diabetic nephropathy. PMID: 25133193
16. Fibroblasts from two long-lived mice mutants (Snell dwarf and PAPP-A knockout) expressed higher levels of TRB3 (a ATF4 target gene) during stress, suggesting a connection to longevity. PMID: 24691093
17. TRB3(-/-) islets show a decrease in both the amplitude and duration of cytokine-stimulated MLK3 induction and JNK activation. PMID: 25204656
18. Trib3 is upregulated in the mouse anterior piriform cortex in response to leucine-deficient diet. Deletion of Trib3 does not influence the rejection of amino acid-imbalanced diet. Trib3 is dispensable for spatial and reversal learning. PMID: 24732777
19. These findings suggest that TRB3 was involved in lipoapoptosis of INS-1 beta cell PMID: 24824999
20. show in renal tubular cells that TRB3 binds to mTOR and the rapamycin-insensitive companion of mTOR (Rictor), a protein specific to mTORC2 PMID: 24676635
21. TRB3 regulates muscle fiber type via a peroxisome proliferator-activated receptor-alpha (PPAR-alpha)-regulated miR499/miR208b pathway, revealing a novel function for TRB3 in the regulation of skeletal muscle fiber type and exercise capacity. PMID: 24740654
22. Data indicate that responding to Toll-like receptor 2 (TLR2)-specific stimulation, the expressions of cell death inducible putative kinase (NIPK) was significantly elevated. PMID: 25108431
23. TRIB3 mediated ER stress-induced beta-cell apoptosis via the NF-kappaB pathway. PMID: 24746137
24. observations presented here strongly support that TRIB3 plays a crucial role on THC anti-neoplastic activity PMID: 23567453
25. Trib3 mRNA expression in bone-marrow-derived mast cells is upregulated by IL-3. Degranulation & activation-induced cytokine mRNA expression are impaired in Trib3-deficient BMMCs. PMID: 23261831
26. TRB3 increased in diabetic testis and further increased in the testis of diabetic mice with Zn deficiency. PMID: 22000581
27. Silence of TRIB3 would diminish atherosclerotic burden and increase the plaque stability in diabetic mice. PMID: 22275087
28. emodin induces BV-2 cell apoptosis through TRB3 and consequently eliminates inflammatory microglia. PMID: 21275776
29. HHcy impairs hepatic glycogen synthesis by inducing the expression of TRB3 PMID: 21435438
30. the GCN2/eIF2alpha/ATF4 pathway is essential for the induction of the TRB3 gene transcription PMID: 21203563
31. enhanced reactive oxygen species and/or free fatty acids associated with the diabetic milieu induce podocyte C/EBP homologous protein and TRB3 expression PMID: 20660016
32. The pseudokinase tribbles homolog 3 interacts with ATF4 to negatively regulate insulin exocytosis in human and mouse beta cells. PMID: 20592469
33. MLK3 mediates its effects via the pseudokinase TRB3, a mammalian homolog of Drosophila Tribbles. PMID: 20421299
34. These data identify TRIB3 induction as a novel molecular mechanism in human insulin resistance and diabetes. PMID: 19996382
35. acute exercise reverses TRB3 expression and insulin signalling restoration in muscle PMID: 19681769
36. Knockdown of hepatic TRB-3 expression improved glucose tolerance, whereas hepatic overexpression of TRB-3 reversed the insulin-sensitive phenotype of PGC-1-deficient mice. PMID: 15107844
37. The combination of elevated TRB3 and constitutive hepatic p70 S6 kinase activity results in decreased insulin signaling via the insulin receptor substrate-1 protein/phosphatidylinositol 3-kinase/Akt pathway. PMID: 16887816
38. Results indicated that TRB3 plays a critical role in muscle differentiation. PMID: 17207467
39. Deletion of Trib3 has minimal effect on insulin-induced Akt activation in hepatic tissue. PMID: 17303803
40. Data show that TRB3 is an important negative regulator of adipogenesis that acts at an early step in the differentiation cascade to block the C/EBPbeta proadipogenic function. PMID: 17646392
41. TRB3 acts as a potent negative regulator of PPARgamma, a master regulator of adipocyte differentiation, and tightly controls adipogenesis PMID: 18187772
42. Data show that C/EBPbeta expression induced by insulin preceded that of TRB3 and that mutation of the C/EBPbeta binding site in TRB3 promoter abolished the responsiveness of the TRB3 gene to insulin. PMID: 19164449
43. TRB3 expression was reduced in the hepatic tissue from diet-induced obesity (Swiss) and leptin-deficient (ob/ob) mice, when compared with respective control groups at rest. PMID: 19492410
44. PPARalpha ligands may reduce cellular number by augmenting TRB3 expression, which in turn induces cell cycle arrest by reducing the expression of Cyclin B1. PMID: 19748123

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KEGG: mmu:228775

STRING: 10090.ENSMUSP00000041747

UniGene: Mm.276018