E3 ubiquitin-protein ligase COP1

Definition:

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. Upon binding to TRIB1, ubiquitinates CEBPA, which lacks a canonical COP1-binding motif (Probable).

References:

[1]. Elisabetta Bianchi, et al. 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. [Content Brief]

[2]. Da-Qiang Li, et al. MTA1 coregulator regulates p53 stability and function. J Biol Chem. 2009 Dec 11;284(50):34545-52. [Content Brief]

[3]. Sacha Uljon, et al. Structural Basis for Substrate Selectivity of the E3 Ligase COP1. Structure. 2016 May 3;24(5):687-696. [Content Brief]

[4]. David Dornan, et al. The ubiquitin ligase COP1 is a critical negative regulator of p53. Nature. 2004 May 6;429(6987):86-92. [Content Brief]

[5]. Ingrid E Wertz, et al. Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase. Science. 2004 Feb 27;303(5662):1371-4. [Content Brief]

[6]. Da-Qiang Li, et al. 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. [Content Brief]

[7]. H H Choi, et al. COP9 signalosome subunit 6 stabilizes COP1, which functions as an E3 ubiquitin ligase for 14-3-3σ. Oncogene. 2011 Dec 1;30(48):4791-801. [Content Brief]

[8]. Chunling Yi, et al. 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. [Content Brief]

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