Tribbles pseudokinase 3 (TRIB3) (TRIB3)

Tribbles pseudokinase 3 (TRIB3) is a member of the Tribbles family of proteins that functions as a molecular scaffold to regulate various intracellular signaling cascades (UniProt Q96RU7). Unlike typical kinases, TRIB3 lacks catalytic activity but modulates signaling by binding to key proteins, most notably the kinase AKT, thereby inhibiting its phosphorylation and downstream activity (Du et al., Science 2003, PMID: 14585963). TRIB3 expression is highly sensitive to cellular stress, including endoplasmic reticulum (ER) stress and nutrient deprivation, and is primarily regulated by the ATF4-CHOP transcription factor axis (Ohoka et al., EMBO J 2005, PMID: 15706348). In clinical contexts, TRIB3 is frequently overexpressed in various cancers, where it promotes tumor cell survival, metastasis, and resistance to chemotherapy (Erazo et al., Cancer Res 2016, PMID: 26455324). Additionally, its role in inhibiting insulin signaling makes it a significant contributor to the development of insulin resistance and type 2 diabetes (Zhang et al., Trends Pharmacol Sci 2018, PMID: 30104616). Therapeutic strategies targeting TRIB3 mRNA, such as siRNAs or antisense oligonucleotides, aim to reduce its expression to restore metabolic balance or sensitize cancer cells to treatment (Salazar et al., J Clin Invest 2009, PMID: 19411761).

Other names

TRB3SKIP3C20orf97NIPKSINKTribbles homolog 3

RNA interference-mediated degradation of TRIB3 mRNA, antisense-mediated inhibition of TRIB3 translation, and disruption of TRIB3-protein interactions (Zhang et al., 2018, PMID: 30104616).