Tribbles homolog 2 is an atypical protein kinase that is encoded in human by the TRIB2 gene.[5][6][7][8] TRIB2 is a pseudokinase member of the (pseudoenzyme) class of signaling/scaffold proteins, possessing very low vestigial catalytic output in vitro and critical scaffolding signaling functions in cells.[9] It is known to signal to canonical MAPK and AKT pathways and to regulate the ubiquitination of substrates with important functions in cell proliferation that control the cell ccyle. It has also been associated with various diseases, especially in human and murine blood and solid tumor models.[10] Like TRIB1 and TRIB3, TRIB2 has recently been considered as a potential allosteric drug target,[11] and its three dimensional structure has been solved with the aid of stabilizing nanobodies [12] corroborating the potential for new approaches for drug targeting outside the highly degraded ATP site [13] and is a putative regulator of cancer-associated signalling and survival through AKT pSer473 modulation.[14] Recent work has established a convincing link between targetable overexpression of TRIB2 and prostate cancer drug responses [15]
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Foulkes DM, Byrne DP, Eyers PA (2015). "Tribbles pseudokinases: novel targets for chemical biology and drug discovery?". Biochemical Society Transactions. 43 (5): 1095–1103. doi:10.1042/BST20150109. PMID 26517930.
Jamieson SA, Pudjihartono M, Horne CR, Viloria JS, Dunlop JL, McMillan HD, Day RC, Keeshan K, Murphy JM, Mace PD (2022). "Nanobodies identify an activated state of the TRIB2 pseudokinase". Structure. 30 (11): 1518–1529. doi:10.1016/j.str.2022.08.006. PMID 36108635.
Foulkes DM, Byrne DP, Yeun W, Shrestha S, Bailey FP, Ferries S, Eyers CE, Keeshan K, Wells C, Drewry DH, Zuercher WJ, Kannan N, Eyers PA (2018). "Covalent inhibitors of EGFR family protein kinases induce degradation of human Tribbles 2 (TRIB2) pseudokinase in cancer cells". Science Signaling. 11: 14687. doi:10.1126/scisignal.aat795. PMID 28276427.
Monga J, Valeriote F, Hwang C, Gadgeel S, Ghosh J (2023). "Daclatasvir, an Antiviral Drug, Downregulates Tribbles 2 Pseudokinase and Resensitizes Enzalutamide-Resistant Prostate Cancer Cells". Molecular Cancer Therapeutics. 22: 381–392. doi:10.1126/scisignal.aat795. PMID 28276427.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Kiss-Toth E, Bagstaff SM, Sung HY, et al. (2004). "Human tribbles, a protein family controlling mitogen-activated protein kinase cascades" (PDF). J. Biol. Chem. 279 (41): 42703–8. doi:10.1074/jbc.M407732200. PMID 15299019. S2CID 25829757.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Hillier LW, Graves TA, Fulton RS, et al. (2005). "Generation and annotation of the DNA sequences of human chromosomes 2 and 4". Nature. 434 (7034): 724–31. Bibcode:2005Natur.434..724H. doi:10.1038/nature03466. PMID 15815621.
- Zhang Y, Davis JL, Li W (2005). "Identification of tribbles homolog 2 as an autoantigen in autoimmune uveitis by phage display". Mol. Immunol. 42 (11): 1275–81. doi:10.1016/j.molimm.2004.11.020. PMID 15950723.
- Lim J, Hao T, Shaw C, et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569. S2CID 13709685.
- Lin KR, Lee SF, Hung CM, et al. (2007). "Survival factor withdrawal-induced apoptosis of TF-1 cells involves a TRB2-Mcl-1 axis-dependent pathway". J. Biol. Chem. 282 (30): 21962–72. doi:10.1074/jbc.M701663200. PMID 17545167.