Tribbles homolog 1 is a protein kinase that in humans is encoded by the TRIB1 gene.[5][6][7] Orthologs of this protein pseudokinase (pseudoenzyme) can be found almost ubiquitously throughout the animal kingdom.[8] It exerts its biological functions through binding to signalling proteins of the MAPKK level of the MAPK pathway, therefore eliciting a regulatory role in the function of this pathway which mediates proliferation, apoptosis and differentiation in cells. Tribbles-1 is encoded by the trib1 gene, which in humans can be found on chromosome 8 at position 24.13 on the longest arm (q). Recent crystal structures show that Tribbles 1 has an unusual 3D structure, containing a 'broken' C-helix region, a binding site for ubiquitinated substrates such as C/EBPalpha and a key regulatory C-tail region.[9] Like TRIB2 and TRIB3, TRIB1 has recently been considered as a potential allosteric drug target.[10]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000173334 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032501 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Wilkin F, Suarez-Huerta N, Robaye B, Peetermans J, Libert F, Dumont JE, Maenhaut C (September 1997). "Characterization of a phosphoprotein whose mRNA is regulated by the mitogenic pathways in dog thyroid cells". European Journal of Biochemistry. 248 (3): 660–8. doi:10.1111/j.1432-1033.1997.t01-1-00660.x. PMID 9342215.
- ^ Hegedus Z, Czibula A, Kiss-Toth E (July 2006). "Tribbles: novel regulators of cell function; evolutionary aspects". Cellular and Molecular Life Sciences. 63 (14): 1632–41. doi:10.1007/s00018-006-6007-9. PMC 11136108. PMID 16715410. S2CID 24556931.
- ^ "Entrez Gene: TRIB1 tribbles homolog 1 (Drosophila)".
- ^ Eyers PA, Keeshan K, Kannan N (April 2017). "Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease". Trends in Cell Biology. 27 (4): 284–298. doi:10.1016/j.tcb.2016.11.002. PMC 5382568. PMID 27908682.
- ^ Murphy JM, Nakatani Y, Jamieson SA, Dai W, Lucet IS, Mace PD (November 2015). "Molecular Mechanism of CCAAT-Enhancer Binding Protein Recruitment by the TRIB1 Pseudokinase". Structure. 23 (11): 2111–21. doi:10.1016/j.str.2015.08.017. PMID 26455797.
- ^ Foulkes DM, Byrne DP, Bailey FP, Eyers PA (October 2015). "Tribbles pseudokinases: novel targets for chemical biology and drug discovery?". Biochemical Society Transactions. 43 (5): 1095–103. doi:10.1042/BST20150109. PMID 26517930.