Biology:TRIB2
 Generic protein structure example |
Tribbles homolog 2 is an atypical protein kinase that is encoded in human by the TRIB2 gene.[1][2][3][4] 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.[5] 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 cycle. It has also been associated with various diseases, especially in human and murine blood and solid tumor models.[6] Like TRIB1 and TRIB3, TRIB2 has recently been considered as a potential allosteric drug target,[7] and its three dimensional structure has been solved with the aid of stabilizing nanobodies [8] corroborating the potential for new approaches for drug targeting outside the highly degraded ATP site [9] and is a putative regulator of cancer-associated signalling and survival through AKT pSer473 modulation.[10] Recent work has established a convincing link between targetable overexpression of TRIB2 and prostate cancer drug responses [11]
References
- ↑ "SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription". J Biol Chem 278 (29): 27072–9. Jul 2003. doi:10.1074/jbc.M209814200. PMID 12736262.
- ↑ "Tribbles homolog 2 inactivates C/EBPalpha and causes acute myelogenous leukemia". Cancer Cell 10 (5): 401–11. Nov 2006. doi:10.1016/j.ccr.2006.09.012. PMID 17097562.
- ↑ "Tribbles: novel regulators of cell function; evolutionary aspects". Cell Mol Life Sci 63 (14): 1632–41. Aug 2006. doi:10.1007/s00018-006-6007-9. PMID 16715410.
- ↑ "Entrez Gene: TRIB2 tribbles homolog 2 (Drosophila)". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=28951.
- ↑ "The Tribbles 2 (TRB2) pseudokinase binds to ATP and autophosphorylate very weakly in a metal-independent manner.". Biochemical Society Transactions 467 (1): 47–62. 2015. doi:10.1042/BJ20141441. PMID 25583260.
- ↑ "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. doi:10.1016/j.tcb.2016.11.002. PMID 27908682.
- ↑ "Tribbles pseudokinases: novel targets for chemical biology and drug discovery?". Biochemical Society Transactions 43 (5): 1095–1103. 2015. doi:10.1042/BST20150109. PMID 26517930.
- ↑ "Nanobodies identify an activated state of the TRIB2 pseudokinase". Structure 30 (11): 1518–1529. 2022. doi:10.1016/j.str.2022.08.006. PMID 36108635.
- ↑ "Pseudokinases: update on their functions and evaluation as new drug targets.". Future Medicinal Chemistry 9 (2): 245–265. 2017. doi:10.4155/fmc-2016-0207. PMID 28097887.
- ↑ "Covalent inhibitors of EGFR family protein kinases induce degradation of human Tribbles 2 (TRIB2) pseudokinase in cancer cells". Science Signaling 11 (549): 14687. 2018. doi:10.1126/scisignal.aat7951. PMID 30254057.
- ↑ "Daclatasvir, an Antiviral Drug, Downregulates Tribbles 2 Pseudokinase and Resensitizes Enzalutamide-Resistant Prostate Cancer Cells". Molecular Cancer Therapeutics 22 (3): 381–392. 2023. doi:10.1158/1535-7163.mct-21-1002. PMID 36805730.
Further reading
- "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. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Human tribbles, a protein family controlling mitogen-activated protein kinase cascades.". J. Biol. Chem. 279 (41): 42703–8. 2004. doi:10.1074/jbc.M407732200. PMID 15299019. http://www.tara.tcd.ie/bitstream/2262/33449/1/Human%20tribbles%2c%20a%20protein%20family%20controlling%20mitogen-activated%20protein%20kinase%20cascades.pdf.
- "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
- "Generation and annotation of the DNA sequences of human chromosomes 2 and 4.". Nature 434 (7034): 724–31. 2005. doi:10.1038/nature03466. PMID 15815621. Bibcode: 2005Natur.434..724H.
- "Identification of tribbles homolog 2 as an autoantigen in autoimmune uveitis by phage display.". Mol. Immunol. 42 (11): 1275–81. 2005. doi:10.1016/j.molimm.2004.11.020. PMID 15950723.
- "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration.". Cell 125 (4): 801–14. 2006. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
- "Survival factor withdrawal-induced apoptosis of TF-1 cells involves a TRB2-Mcl-1 axis-dependent pathway.". J. Biol. Chem. 282 (30): 21962–72. 2007. doi:10.1074/jbc.M701663200. PMID 17545167.
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