TRIB3 explained

Tribbles homolog 3 is a protein that in humans is encoded by the TRIB3 gene.^{[1] [2] [3]}

Function

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.^{[4] [5]}

Interactions

TRIB3 has been shown to interact with:

• AKT1,
• CSNK2B,^[6]
• Fibronectin^[6]
• MCM3AP,^[7]
• RELA,^[8]
• SIAH1,^[6] and
• TIAF1.^[6]

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Deloukas P, Matthews LH, Ashurst J, etal . The DNA sequence and comparative analysis of human chromosome 20. . Nature . 414 . 6866 . 865–71 . 2002 . 11780052 . 10.1038/414865a . 2001Natur.414..865D . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Wu M, Xu LG, Zhai Z, Shu HB . SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription. . J. Biol. Chem. . 278 . 29 . 27072–9 . 2003 . 12736262 . 10.1074/jbc.M209814200 . free.
• Bowers AJ, Scully S, Boylan JF . SKIP3, a novel Drosophila tribbles ortholog, is overexpressed in human tumors and is regulated by hypoxia. . Oncogene . 22 . 18 . 2823–35 . 2003 . 12743605 . 10.1038/sj.onc.1206367 . free .
• Huang J, Teng L, Liu T, etal . Identification of a novel serine/threonine kinase that inhibits TNF-induced NF-kappaB activation and p53-induced transcription. . Biochem. Biophys. Res. Commun. . 309 . 4 . 774–8 . 2003 . 13679039 . 10.1016/j.bbrc.2003.08.069 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Kiss-Toth E, Bagstaff SM, Sung HY, etal . Human tribbles, a protein family controlling mitogen-activated protein kinase cascades. . J. Biol. Chem. . 279 . 41 . 42703–8 . 2004 . 15299019 . 10.1074/jbc.M407732200 . free . 2262/33449 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Ohoka N, Yoshii S, Hattori T, etal . TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. . EMBO J. . 24 . 6 . 1243–55 . 2005 . 15775988 . 10.1038/sj.emboj.7600596 . 556400 .
• Ord D, Ord T . Characterization of human NIPK (TRB3, SKIP3) gene activation in stressful conditions. . Biochem. Biophys. Res. Commun. . 330 . 1 . 210–8 . 2005 . 15781252 . 10.1016/j.bbrc.2005.02.149 .
• Prudente S, Hribal ML, Flex E, etal . The functional Q84R polymorphism of mammalian Tribbles homolog TRB3 is associated with insulin resistance and related cardiovascular risk in Caucasians from Italy. . Diabetes . 54 . 9 . 2807–11 . 2005 . 16123373 . 10.2337/diabetes.54.9.2807 . free .
• Schwarzer R, Dames S, Tondera D, etal . TRB3 is a PI 3-kinase dependent indicator for nutrient starvation. . Cell. Signal. . 18 . 6 . 899–909 . 2006 . 16129579 . 10.1016/j.cellsig.2005.08.002 .
• Stelzl U, Worm U, Lalowski M, etal . A human protein-protein interaction network: a resource for annotating the proteome. . Cell . 122 . 6 . 957–68 . 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . 11858/00-001M-0000-0010-8592-0 . 8235923 . free .
• Matsushima R, Harada N, Webster NJ, etal . Effect of TRB3 on insulin and nutrient-stimulated hepatic p70 S6 kinase activity. . J. Biol. Chem. . 281 . 40 . 29719–29 . 2006 . 16887816 . 10.1074/jbc.M511636200 . free .
• Koh HJ, Arnolds DE, Fujii N, etal . Skeletal muscle-selective knockout of LKB1 increases insulin sensitivity, improves glucose homeostasis, and decreases TRB3. . Mol. Cell. Biol. . 26 . 22 . 8217–27 . 2007 . 16966378 . 10.1128/MCB.00979-06 . 1636784 .

Notes and References

1. Du K, Herzig S, Kulkarni RN, Montminy M . TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver . Science . 300 . 5625 . 1574–7 . Jun 2003 . 12791994 . 10.1126/science.1079817 . 2003Sci...300.1574D . 43360696 .
2. Hegedus Z, Czibula A, Kiss-Toth E . Tribbles: novel regulators of cell function; evolutionary aspects . Cell Mol Life Sci . 63 . 14 . 1632–41 . Aug 2006 . 16715410 . 10.1007/s00018-006-6007-9 . 24556931 . 11136108 .
3. Web site: Entrez Gene: TRIB3 tribbles homolog 3 (Drosophila).
4. Eyers PA, Keeshan K, Kannan N . Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease. . Trends in Cell Biology . 27 . 9 . S0962-8924(16)30178-7 . 2016 . 27908682 . 10.1016/j.tcb.2016.11.002. 5382568.
5. Foulkes DM, Byrne DP, Eyers PA . Tribbles pseudokinases: novel targets for chemical biology and drug discovery? . Biochemical Society Transactions . 43 . 5 . 1095–1103 . 2015 . 26517930 . 10.1042/BST20150109.
6. Zhou Y, Li L, Liu Q, Xing G, Kuai X, Sun J, Yin X, Wang J, Zhang L, He F . E3 ubiquitin ligase SIAH1 mediates ubiquitination and degradation of TRB3 . Cell. Signal. . 20 . 5 . 942–8 . May 2008 . 18276110 . 10.1016/j.cellsig.2008.01.010 .
7. Bowers AJ, Scully S, Boylan JF . SKIP3, a novel Drosophila tribbles ortholog, is overexpressed in human tumors and is regulated by hypoxia . Oncogene . 22 . 18 . 2823–35 . May 2003 . 12743605 . 10.1038/sj.onc.1206367 . free .
8. Wu M, Xu LG, Zhai Z, Shu HB . SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription . J. Biol. Chem. . 278 . 29 . 27072–9 . July 2003 . 12736262 . 10.1074/jbc.M209814200 . free.