Xin-Hua Feng, Molecular and Cellular Biology: Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling and Mesenchymal St

文章出处: 作者: 发布时间: 2015-04-03 访问次数: 86
On March 9, 2015, Dr. Feng’s research group published a paper online entitled “Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling and Mesenchymal Stem Cell Differentiation” in Molecular and Cellular Biology (MCB).
 
Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance and differentiation. BMPs can induce osteogenesis and inhibit myogenesis of mesenchymalstem cells. Canonical BMP signaling is stringently controlled through reversible phosphorylation and nucleocytoplasmic shuttling of Smad1, Smad5, and Smad8 (Smad1/5/8). However, how the nuclear export of Smad1/5/8 is regulated remains unclear. In this study, Dr. Feng’ group reported the identification and characterization of a new Ran binding protein called RanBP3L that mediated the nuclear export of BMP-specific R-Smads. RanBP3L directly recognizes dephosphorylated Smad1/5/8 and mediates their nuclear export in a Ran dependent manner. Increased expression of RanBP3L blocks BMP-induced osteogenesis of mouse bone marrow-derived mesenchymalstem cells and promotes myogenic induction of C2C12 mouse myoblasts, whereas depletion of RanBP3L expression enhances BMP-dependent stem cell differentiation activity and transcriptional responses. In conclusion, RanBP3L, as a nuclear exporter for BMP-specific Smads, plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation. 
 
PhD candidate Fenfang Chen from Dr. Feng’s lab is the first author of this paper. This research was done by collaboration with Baylor College of Medicine and was partly supported by grants from MOST(2012CB966600), NSFC (31090360), the NIH (R01AR053591,R01GM63773, R01CA108454, and R01DK073932), the 111 Project(B13026), Project 985, and Fundamental Research Funds for the CentralUniversities.