Tribbles homolog 3

Definition:

Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress. Inhibits the transcriptional activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER stress. May play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells. 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 (By similarity). Disrupts insulin signaling by binding directly to Akt kinases and blocking their activation (By similarity). May bind directly to and mask the 'Thr-308' phosphorylation site in AKT1 (By similarity). Interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity. Interacts with MAPK kinases and regulates activation of MAP kinases. Can inhibit APOBEC3A editing of nuclear DNA.

References:

[1]. Min Wu, et al. SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription. J Biol Chem. 2003 Jul 18;278(29):27072-9. [Content Brief]

[2]. Marie-Ming Aynaud, et al. Human Tribbles 3 protects nuclear DNA from cytidine deamination by APOBEC3A. J Biol Chem. 2012 Nov 9;287(46):39182-92. [Content Brief]

[3]. Endre Kiss-Toth, et al. Human tribbles, a protein family controlling mitogen-activated protein kinase cascades. J Biol Chem. 2004 Oct 8;279(41):42703-8. [Content Brief]

[4]. Daima Ord, et al. Characterization of human NIPK (TRB3, SKIP3) gene activation in stressful conditions. Biochem Biophys Res Commun. 2005 Apr 29;330(1):210-8. [Content Brief]

[5]. Nobumichi Ohoka, et al. TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. EMBO J. 2005 Mar 23;24(6):1243-55. [Content Brief]

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