Tribbles homolog 2 is an atypical protein kinase that is encoded in human by the TRIB2gene.[1][2][3][4] TRIB2 is a pseudokinase member of the (pseudoenzyme) class of signaling/scaffold proteins, possessing little vestigial catalytic output in vitro.[5] It is known to signal to canonical MAPK pathways and to regulate the ubiquitination of substrates with important functions in the immune system. It has also been associated with various diseases, especially in vertebrate leukaemia models.[6] Like TRIB1 and TRIB3, TRIB2 has recently been considered as a potential allosteric drug target,[7][8] and is a putative regulator of cancer-associated signalling and survival through AKT pSer473 modulation [9]
References
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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. PMID26517930.
↑Byrne DP, Foulkes DM, Eyers PA (2017). "Pseudokinases: update on their functions and evaluation as new drug targets". Future Medicinal Chemistry. 9 (2): 245–265. doi:10.4155/fmc-2016-0207. PMID28097887.
Kiss-Toth E, Bagstaff SM, Sung HY, et al. (2004). "Human tribbles, a protein family controlling mitogen-activated protein kinase cascades". J. Biol. Chem. 279 (41): 42703–8. doi:10.1074/jbc.M407732200. PMID15299019.
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. doi:10.1038/nature03466. PMID15815621.
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. PMID15950723.
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. PMID16713569.
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. PMID17545167.
