TRIB3

Description

The TRIB3 (tribbles pseudokinase 3) is a protein-coding gene located on chromosome 20.

Tribbles homolog 3 is a protein that in humans is encoded by the TRIB3 gene. The protein encoded by this gene is a putative protein kinase that is induced by the transcription factor NF-kappaB. It is a pseudoenzyme that is thought to be a negative regulator of NF-kappaB, and can also sensitize cells to TNF- and TRAIL-induced apoptosis. In addition, this protein has been reported to negatively regulate the cell survival serine-threonine kinase AKT1. TRIB3 has recently been associated with neuronal signalling, and like TRIB1 and TRIB2, could be considered as a potential allosteric drug target. TRIB3 has been shown to interact with: AKT1, CSNK2B, Fibronectin, MCM3AP, RELA, SIAH1, and TIAF1.

TRIB3 is an inactive protein kinase that acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress. It inhibits the transcriptional activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER stress. TRIB3 may play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells. TRIB3 acts as a negative feedback regulator of the ATF4-dependent transcription during the ISR: while TRIB3 expression is promoted by ATF4, TRIB3 protein interacts with ATF4 and inhibits ATF4 transcription activity. TRIB3 disrupts insulin signaling by binding directly to Akt kinases and blocking their activation. It may bind directly to and mask the 'Thr-308' phosphorylation site in AKT1. TRIB3 interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity. It interacts with MAPK kinases and regulates activation of MAP kinases. TRIB3 can inhibit APOBEC3A editing of nuclear DNA.

TRIB3 is also known as C20orf97, NIPK, SINK, SKIP3, TRB3.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing