| Structural highlights
Function
[RFWD2_HUMAN] E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Involved in JUN ubiquitination and degradation. Directly involved in p53 (TP53) ubiquitination and degradation, thereby abolishing p53-dependent transcription and apoptosis. Ubiquitinates p53 independently of MDM2 or RCHY1. Probably mediates E3 ubiquitin ligase activity by functioning as the essential RING domain subunit of larger E3 complexes. In contrast, it does not constitute the catalytic RING subunit in the DCX DET1-COP1 complex that negatively regulates JUN, the ubiquitin ligase activity being mediated by RBX1. Involved in 14-3-3 protein sigma/SFN ubiquitination and proteasomal degradation, leading to AKT activation and promotion of cell survival. Ubiquitinates MTA1 leading to its proteasomal degradation.[1] [2] [3] [4] [5] [6] [7] [TRIB1_HUMAN] Interacts with MAPK kinases and regulates activation of MAP kinases. May not display kinase activity.[8] [9]
Publication Abstract from PubMed
COP1 proteins are E3 ubiquitin ligases that regulate phototropism in plants and target transcription factors for degradation in mammals. The substrate-binding region of COP1 resides within a WD40-repeat domain that also binds to Trib proteins, which are adaptors for C/EBPalpha degradation. Here we report structures of the human COP1 WD40 domain in isolation, and complexes of the human and Arabidopsis thaliana COP1 WD40 domains with the binding motif of Trib1. The human and Arabidopsis WD40 domains are seven-bladed beta propellers with an inserted loop on the bottom face of the first blade. The Trib1 peptide binds in an extended conformation to a highly conserved surface on the top face of the beta propeller, indicating a general mode for recognition of peptide motifs by COP1. Together, these studies identify the structural basis and key interactions for motif recognition by COP1, and hint at how Trib1 autoinhibition is overcome to target C/EBPalpha for degradation.
Structural Basis for Substrate Selectivity of the E3 Ligase COP1.,Uljon S, Xu X, Durzynska I, Stein S, Adelmant G, Marto JA, Pear WS, Blacklow SC Structure. 2016 May 3;24(5):687-96. doi: 10.1016/j.str.2016.03.002. Epub 2016 Mar, 31. PMID:27041596[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yi C, Wang H, Wei N, Deng XW. An initial biochemical and cell biological characterization of the mammalian homologue of a central plant developmental switch, COP1. BMC Cell Biol. 2002 Dec 4;3:30. Epub 2002 Dec 4. PMID:12466024
- ↑ Bianchi E, Denti S, Catena R, Rossetti G, Polo S, Gasparian S, Putignano S, Rogge L, Pardi R. Characterization of human constitutive photomorphogenesis protein 1, a RING finger ubiquitin ligase that interacts with Jun transcription factors and modulates their transcriptional activity. J Biol Chem. 2003 May 30;278(22):19682-90. Epub 2003 Mar 3. PMID:12615916 doi:http://dx.doi.org/10.1074/jbc.M212681200
- ↑ Wertz IE, O'Rourke KM, Zhang Z, Dornan D, Arnott D, Deshaies RJ, Dixit VM. Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase. Science. 2004 Feb 27;303(5662):1371-4. Epub 2004 Jan 22. PMID:14739464 doi:10.1126/science.1093549
- ↑ Dornan D, Wertz I, Shimizu H, Arnott D, Frantz GD, Dowd P, O'Rourke K, Koeppen H, Dixit VM. The ubiquitin ligase COP1 is a critical negative regulator of p53. Nature. 2004 May 6;429(6987):86-92. Epub 2004 Apr 21. PMID:15103385 doi:http://dx.doi.org/10.1038/nature02514
- ↑ Li DQ, Ohshiro K, Reddy SD, Pakala SB, Lee MH, Zhang Y, Rayala SK, Kumar R. E3 ubiquitin ligase COP1 regulates the stability and functions of MTA1. Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17493-8. Epub 2009 Sep 24. PMID:19805145 doi:http://dx.doi.org/0908027106
- ↑ Li DQ, Divijendra Natha Reddy S, Pakala SB, Wu X, Zhang Y, Rayala SK, Kumar R. MTA1 coregulator regulates p53 stability and function. J Biol Chem. 2009 Dec 11;284(50):34545-52. doi: 10.1074/jbc.M109.056499. Epub, 2009 Oct 16. PMID:19837670 doi:http://dx.doi.org/10.1074/jbc.M109.056499
- ↑ Choi HH, Gully C, Su CH, Velazquez-Torres G, Chou PC, Tseng C, Zhao R, Phan L, Shaiken T, Chen J, Yeung SC, Lee MH. COP9 signalosome subunit 6 stabilizes COP1, which functions as an E3 ubiquitin ligase for 14-3-3sigma. Oncogene. 2011 Dec 1;30(48):4791-801. doi: 10.1038/onc.2011.192. Epub 2011 May, 30. PMID:21625211 doi:http://dx.doi.org/10.1038/onc.2011.192
- ↑ Kiss-Toth E, Bagstaff SM, Sung HY, Jozsa V, Dempsey C, Caunt JC, Oxley KM, Wyllie DH, Polgar T, Harte M, O'neill LA, Qwarnstrom EE, Dower SK. Human tribbles, a protein family controlling mitogen-activated protein kinase cascades. J Biol Chem. 2004 Oct 8;279(41):42703-8. Epub 2004 Aug 6. PMID:15299019 doi:http://dx.doi.org/10.1074/jbc.M407732200
- ↑ Kiss-Toth E, Bagstaff SM, Sung HY, Jozsa V, Dempsey C, Caunt JC, Oxley KM, Wyllie DH, Polgar T, Harte M, O'neill LA, Qwarnstrom EE, Dower SK. Human tribbles, a protein family controlling mitogen-activated protein kinase cascades. J Biol Chem. 2004 Oct 8;279(41):42703-8. Epub 2004 Aug 6. PMID:15299019 doi:http://dx.doi.org/10.1074/jbc.M407732200
- ↑ Uljon S, Xu X, Durzynska I, Stein S, Adelmant G, Marto JA, Pear WS, Blacklow SC. Structural Basis for Substrate Selectivity of the E3 Ligase COP1. Structure. 2016 May 3;24(5):687-96. doi: 10.1016/j.str.2016.03.002. Epub 2016 Mar, 31. PMID:27041596 doi:http://dx.doi.org/10.1016/j.str.2016.03.002
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