E3 ubiquitin-protein ligase SMURF2

Definition:

E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Interacts with SMAD7 to trigger SMAD7-mediated transforming growth factor beta/TGF-beta receptor ubiquitin-dependent degradation, thereby down-regulating TGF-beta signaling. In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with AIMP1. Also forms a stable complex with TGF-beta receptor-mediated phosphorylated SMAD1, SMAD2 and SMAD3, and targets SMAD1 and SMAD2 for ubiquitination and proteasome-mediated degradation. SMAD2 may recruit substrates, such as SNON, for ubiquitin-dependent degradation. Negatively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation.; (Microbial infection) In case of filoviruses Ebola/EBOV and Marburg/MARV infection, the complex formed by viral matrix protein VP40 and SMURF2 facilitates virus budding.

References:

[1]. Y Zhang, et al. Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase. Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):974-9. [Content Brief]

[2]. Gianni M Di Guglielmo, et al. Distinct endocytic pathways regulate TGF-beta receptor signalling and turnover. Nat Cell Biol. 2003 May;5(5):410-21. [Content Brief]

[3]. Yeon Sook Lee, et al. AIMP1/p43 downregulates TGF-beta signaling via stabilization of smurf2. Biochem Biophys Res Commun. 2008 Jul 4;371(3):395-400. [Content Brief]

[4]. Ariel Shepley-McTaggart, et al. Ubiquitin Ligase SMURF2 Interacts with Filovirus VP40 and Promotes Egress of VP40 VLPs. Viruses. 2021 Feb 12;13(2):288. [Content Brief]

[5]. P Kavsak, et al. Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. Mol Cell. 2000 Dec;6(6):1365-75. [Content Brief]

[6]. S Bonni, et al. TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation. Nat Cell Biol. 2001 Jun;3(6):587-95. [Content Brief]

[7]. X Lin, et al. Smurf2 is a ubiquitin E3 ligase mediating proteasome-dependent degradation of Smad2 in transforming growth factor-beta signaling. J Biol Chem. 2000 Nov 24;275(47):36818-22. [Content Brief]

[8]. June-Hyung Kim, et al. TTC3 contributes to TGF-β1-induced epithelial-mesenchymal transition and myofibroblast differentiation, potentially through SMURF2 ubiquitylation and degradation. Cell Death Dis. 2019 Jan 29;10(2):92. [Content Brief]

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