title: Binding of RhoA by the C2 domain of E3 ligase Smurf1 is essential for Smurf1-regulated RhoA ubiquitination and cell protrusive activity.
abstract: Smurf1-mediated RhoA ubiquitination and degradation plays key roles in regulation of cell polarity and protrusive activity. However, how Smurf1 recognizes RhoA is still not clear. Here we report that the C2 domain of Smurf1 is necessary and sufficient for binding RhoA, and therefore is crucial for targeting RhoA for ubiquitination. In contrast, the C2 domain is dispensable for Smurf1-mediated ubiquitination of Smad1. Consistent with its biochemical specificity, the C2 domain is essential for Smurf1-regulated protrusion formation but not BMP signaling. Therefore, our study reveals the mechanism of the C2 domain of Smurf1 in substrate selection.
authors.affiliation: Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Maoyuan
authors.initials: M
authors.lastname: Tian
authors.forename: Chunmei
authors.initials: C
authors.lastname: Bai
authors.forename: Qi
authors.initials: Q
authors.lastname: Lin
authors.forename: Huayue
authors.initials: H
authors.lastname: Lin
authors.forename: Mingdong
authors.initials: M
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Ding
authors.forename: Hong-Rui
authors.initials: HR
authors.lastname: Wang
mesh_terms: D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; C497399:SMAD1 protein, human; D051898:Smad1 Protein; C498342:SMURF1 protein, human; D044767:Ubiquitin-Protein Ligases; D020742:rhoA GTP-Binding Protein