NELL-1 binds to APR3 affecting human osteoblast proliferation and differentiation

• Published in: FEBS letters 2011-08, Vol.585 (15), p.2410-2418
• Main Authors: Zou, Xuan, Shen, Jia, Chen, Feng, Ting, Kang, Zheng, Zhong, Pang, Shen, Zara, Janette N., Adams, John S., Soo, Chia, Zhang, Xinli
• Format: Article
• Language: English
• Subjects: alkaline phosphatase; all-trans-retinoic acid; Alp; Apoptosis Regulatory Proteins - metabolism; Apoptosis related protein 3; APR3; ATRA; bone sialo protein; Bsp; Calcium-Binding Proteins; Cell Differentiation; Cell Proliferation; Cells, Cultured; craniosynostosis; Cyclin D1; Cyclin D1 - metabolism; Human osteoblast; Humans; Nel-like protein 1; NELL-1; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins - physiology; Ocn; Osteoblasts - cytology; Osteoblasts - metabolism; osteocalcin; Peptide Library; Phage display; Protein Binding - physiology; runt-related transcription factor 2; Runx2
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2011.06.024

► We constructed a cDNA library of Saos2 cells to identify NELL-1 interacting proteins. ► APR3 was identified as a direct binding protein of NELL-1 through phage display. ► The inhibitory effect of APR3 on osteoblast proliferation is enhanced by NELL-1. ► NELL-1 and APR3 binding can promote osteoblast differentiation and mineralization. Nel-like protein 1 (NELL-1) is an osteoinductive molecule associated with premature calvarial suture closure. Here we identified apoptosis related protein 3 (APR3), a membrane protein known as a proliferation suppressor, as a binding protein of NELL-1 by biopanning. NELL-1 and APR3 colocalized on the nuclear envelope of human osteoblasts. NELL-1 significantly inhibited proliferation of osteoblasts co-transfected with APR3 through further down-regulation of Cyclin D1. The co-expression of NELL-1 and APR3 enhanced Ocn and Bsp expression and mineralization. RNAi of APR3 significantly reduced the differentiation effect of NELL-1. These findings suggest that the effects of NELL-1 on osteoblastic differentiation and proliferation are partly through binding to APR3. APR3physically interacts with NELL1 by pull down(View interaction) APR3 and NELL1colocalize by fluorescence microscopy(View interaction) NELL1physically interacts with SMEK1 by phage display(View interaction) NELL1physically interacts with EIF4B by phage display(View interaction) NELL1physically interacts with APR3 by anti bait coimmunoprecipitation(View interaction) NELL1physically interacts with EIF5B by phage display(View interaction) NELL1physically interacts with DNTTIP2 by phage display(View interaction) NELL1physically interacts with EEF1A1 by phage display(View interaction) NELL1physically interacts with Nexilin by phage display(View interaction) NELL1physically interacts with PLCG1 by phage display(View interaction) NELL1physically interacts with APR3 by phage display(View interaction) NELL1physically interacts with SLTM by phage display(View interaction) NELL1physically interacts with SSRP1 by phage display(View interaction) NELL1physically interacts with NOL10 by phage display(View interaction)