Background
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 (SMURF1) is a member of the E3 protein ligase family and cloning of the human gene was first described by Zhu et al. (1999). SMURF1 is a HECT domain ubiquitin E3 ligase that has been shown to regulate the cell polarity and protrusive activity and motility of tumour cells. Atypical protein kinase C-zeta (PKCζ), an effector of the Cdc42/Rac1-PAR6 polarity complex, recruits SMURF1 to cellular protrusions where it controls the local level of Rho A through degradation of the Rho A in the lamellipodia and filopodia of the cell (Wang et al., 2003). SMURF1 is also a negative regulator of the Bone Morphogenetic Protein (BMP) signalling pathway mediating the ubiquitylation and degradation of SMAD1 and SMAD5 (Zhu et al., 1999). More recently SMURF1 has been shown to ubiquitylate and degrade Krüppel-like factor 2 (KLF2) a transcription factor essential for normal lung development (Xie et al., 2011).
References
Wang HR, Zhang Y, Ozdamar B, Ogunjimi AA, Alexandrova E, Thomsen GH, Wrana JL (2003) Regulation of cell polarity and protrusion formation by targeting RhoA for degradation. Science 302, 1775-9.
Xie P, Tang Y, Shen S, Wang Y, Xing G, Yin Y, He F, Zhang L (2011) Smurf1 ubiquitin ligase targets Kruppel-like factor KLF2 for ubiquitination and degradation in human lung cancer H1299 cells. Biochem Biophys Res Commun 407, 254-9.
Zhu H, Kavsak P, Abdollah S, Wrana JL, Thomsen GH (1999) A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation. Nature 400, 687-93.