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

Zhejiang California International NanoSystems Institute, Zhejiang University, Hangzhou, PR China.
FEBS letters (Impact Factor: 3.17). 06/2011; 585(15):2410-8. DOI: 10.1016/j.febslet.2011.06.024
Source: PubMed


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.

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Available from: Shen Pang, Mar 18, 2014
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    • "by inhibiting the PI3K-Akt signaling pathway in gastric cancer [24]. While another candidate target NELL was reported to have the capacity to interact with the apoptosis related protein 3 (APR3), thus affecting human osteoblast proliferation and differentiation [25]. And PCBP was reported to act as a negative regulator of mitochondrial antiviral signaling (MAVS) by leading MAVS proteasomal degradation via K48-linked poly ubiquitination [26]. "
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    • "two negative regulators of osteoblast differentiation BMPER and VWC2[39]; EN1, a modulator of osteoblast differentiation and proliferation [40]; DLL3, a notch ligand implicated in human skeletal growth disorders [41]; TCF21, a tumor suppressor that regulates mesenchymal-epithelial cell transitions; and EMCN, a mucin-like anti-adhesion membrane protein and hematopoietic stem cell marker [42]. In a second network, GRAIL connects three genes that regulate bone formation - the osteoblast differentiation enhancer FAM5C[43]; NELL1, a regulator of osteoblast differentiation and ossification [44]; and TNFRSF11A, an essential mediator of osteoclast development [45] - and the pro-apoptotic gene BLID, frequently deleted in human breast, lung, ovarian, and cervical cancers [46]. "
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