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 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] High levels of autoantibodies against TRIB2 in Hcrt neurons (in lateral and posterior hypothalamus) seem also closely related to some cases of narcolepsy + cataplexy (N+C) [10]
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/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=28951.
- ↑ "The Tribbles 2 (TRB2) pseudokinase binds to ATP and autophosphorylates 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.
- ↑ "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.
- ↑ "TRIB2 confers resistance to anti-cancer therapy by activating the serine/threonine protein kinase AKT". Nature Communications 8 (5): 14687. 2017. doi:10.1038/ncomms14687. PMID 28276427. Bibcode: 2017NatCo...814687H.
- ↑ "The trouble with tribbles: donantibodies against TRIB2 cause narcolepsy". Sleep 33 (7): 857–8. 2010. doi:10.1093/sleep/33.7.857. PMID 20614841.
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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