The enzymes of the ubiquitylation pathway play a pivotal role in a number of cellular processes including the regulated and targeted proteasome-dependent degradation of substrate proteins. Three classes of enzymes are involved in the process of ubiquitylation; activating enzymes (E1s), conjugating enzymes (E2s) and protein ligases (E3s). Smad-Specific E3 Ubiquitin Protein Ligase 1 (SMURF2) is a member of the E3 protein ligase family and cloning of the human gene was first described by Kavsak et al. (2000). SMURF2 is a HECT domain ubiquitin E3 ligase that has been shown to regulate cell polarity, senescence and tumor suppression (Blank et al., 2012). Immunoprecipitation studies have demonstrated that SMURF2 interacts with RNF11 through the binding of the WW domain 2 and 3 of SMURF2 to the PY motif of RNF11. RNF11 was also found to interact with Ube2D1 in this complex and ubiquitiylation of both SMURF2 and RNF11 was detected. (Subramaniam et al., 2003). Knock down of SMURF2 in human tumour cell lines results in increased levels of RNF20 and ubiquitylation of the RNF20 substrate histone H2B (Blank et al., 2012). SMURF2 knockout mice appear normal until early adulthood, when a large number of them develop tumours of all types (Blank et al., 2012).
Blank M, Tang Y, Yamashita M, Burkett SS, Cheng SY. et al. (2012) A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20. Nature Med. 18, 227-234.
Kavsak P, Rasmussen RK, Causing CG, Bonni S. et al. (2000) Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF-beta receptor for degradation. Molec Cell 6, 1365-1375.
Subramaniam V, Li H, Wong M, Kitching R, Attisano L, Wrana J, Zubovits J, Burger AM, Seth A. (2003) The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase. Brit J Cancer 89, 1538-1544.