Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling and Mesenchymal Stem Cell Differentiation
| Autor: | Xia Lin, Jiahuai Han, Yanzhen Chen, Pinglong Xu, Xin-Hua Feng, Zhengmao Zhang, Chao Wang, Mu Xiao, Fenfang Chen, Bin Zhao |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Nucleocytoplasmic Transport Proteins animal structures Cellular differentiation Muscle Fibers Skeletal Smad Proteins Biology Bone morphogenetic protein Cell Line Mice Osteogenesis Animals Humans Phosphorylation Nuclear protein Author Correction Nuclear export signal Molecular Biology Cell Nucleus Nuclear Proteins Cell Differentiation Mesenchymal Stem Cells Cell Biology BMPR2 Cell biology Mice Inbred C57BL Bone morphogenetic protein 6 HEK293 Cells Bone Morphogenetic Proteins embryonic structures Mesenchymal stem cell differentiation Stem cell Signal Transduction |
| Zdroj: | Molecular and Cellular Biology. 35:1700-1711 |
| ISSN: | 1098-5549 |
| Popis: | Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance and differentiation. BMPs can induce osteogenesis and inhibit myogenesis of mesenchymal stem 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. Here we report that the Ran-binding protein RanBP3L acts as a nuclear export factor for Smad1/5/8. 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 mesenchymal stem 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, our results demonstrate that RanBP3L, as a nuclear exporter for BMP-specific Smads, plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation. |
| Databáze: | OpenAIRE |
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