Zhang Yue, Wang Hong-Rui, Wrana Jefferey L
Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
Cell Cycle. 2004 Apr;3(4):391-2. doi: 10.4161/cc.3.4.772. Epub 2004 Apr 1.
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.
小GTP酶Rho家族的成员因其在肌动蛋白细胞骨架动态调节中的重要功能而广为人知。我们最近发现，一种名为Smurf1的HECT结构域E3泛素连接酶，通过在细胞突起处靶向RhoA进行降解来调节细胞极性和突起形成。Smurf1作为极性复合体的一个组成部分——蛋白激酶Cxi的伙伴来调节这些功能。此外，利用RNA干扰介导的敲低技术，我们证明了该信号通路对于维持肿瘤细胞的转化形态和运动能力是必需的。因此，Smurf1在细胞定向运动过程中提供了细胞极性控制与泛素介导的RhoA降解之间的联系。在此，我们进一步讨论Smurf1活性空间控制的实现机制以及这些发现对癌症和发育的潜在影响。
