Smurf1: a link between cell polarity and ubiquitination.
Members of the Rho family of small guanosine triphosphatases are well known for their important functions in the dynamic regulation of actin cytoskeleton. We recently found that a HECT domain E3 ubiquitin ligase, called Smurf1, regulates cell polarity and protrusion formation by targeting RhoA for degradation at cellular protrusions. Smurf1 regulates these functions as a partner of protein kinase Cxi, a component of the polarity complex. Furthermore, using siRNA-mediated knockdown, we demonstrated this pathway is required to maintain the transformed morphology and motility of a tumor cell. Smurf1 thus provides a link between the control of cell polarity and ubiquitin-mediated RhoA degradation during directional cell movements. Here we further discuss the mechanism by which the spatial control of Smurf1 activity is accomplished and the potential implications of these findings in cancer and development.
Zhang
Yue
Y
Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
Wang
Hong-Rui
HR
Wrana
Jefferey L
JL
D000818:Animals; D016764:Cell Polarity; D004330:Drosophila; D029721:Drosophila Proteins; D020558:GTP Phosphohydrolases / Q000378:metabolism; D011487:Protein Conformation; D011493:Protein Kinase C / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D014981:Xenopus; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000099221:Protein Kinase C zeta
D029721:Drosophila Proteins; D020558:GTP Phosphohydrolases; D011493:Protein Kinase C; D034741:RNA, Small Interfering; D019089:Stem Cell Factor; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D020741:rho GTP-Binding Proteins; D000099221:Protein Kinase C zeta; C120925:SMURF1 protein, Xenopus; C492378:Smurf protein, Drosophila