Enteropeptidase can cleave trypsinogen on the sequence of Asp-Asp-Asp-Asp-Lys and plays an important role in food digestion. The RANKL-RANK signalling pathway plays a pivotal role in bone remodelling. In this study, we reported that enteropeptidase can inhibit the RANKL-RANK signalling pathway through the cleavage of RANK. A surrogate peptide blocking assay indicated that enteropeptidase could specifically cleave RANK on the sequence NEEDK. Osteoclast differentiation assay and NF-kappa B activity assay confirmed that enteropeptidase could inhibit osteoclastogenesis in vitro through the cleavage of RANK. This is the first study to prove that the RANKL-RANK signalling pathway can be inhibited by cleavage of RANK instead of targeting RANKL. Structured summary of protein interactions: EP cleaves hRANK by cleavage assay (View interaction) EP cleaves mRANK by cleavage assay (View interaction) (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
基金:
Ministry of Science and Technology of ChinaMinistry of Science and Technology, China [2012ZX10004701-001-002]; 973 programNational Basic Research Program of China [2013CB531502]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31070783, 31170829, 81021003, 81270424, 81100550, 81100600, 81041024]; Beijing Natural Science FoundationBeijing Natural Science Foundation [5112022]; China International Medical Foundation (CIMF) - Novo Nordisk China Diabetes Young Scientific Talent Research Funding [2012-25]
第一作者机构:[1]Chinese Acad Sci, CAS Key Lab Pathogen Microbiol & Immunol, Inst Microbiol, Beijing 100101, Peoples R China;[2]Univ Chinese Acad Sci, Beijing, Peoples R China;
通讯作者:
通讯机构:[1]Chinese Acad Sci, CAS Key Lab Pathogen Microbiol & Immunol, Inst Microbiol, Beijing 100101, Peoples R China;[8]Chinese Acad Sci, Ctr Mol Immunol, Inst Microbiol, 1 Beichen West, Beijing 100101, Peoples R China
推荐引用方式(GB/T 7714):
Zhao Yunfeng,Jin Mengmeng,Ma Juan,et al.Inhibition effect of enteropeptidase on RANKL-RANK signalling by cleavage of RANK[J].FEBS LETTERS.2013,587(18):2958-2964.doi:10.1016/j.febslet.2013.08.005.
APA:
Zhao, Yunfeng,Jin, Mengmeng,Ma, Juan,Zhang, Shiqian,Li, Wei...&Gao, Bin.(2013).Inhibition effect of enteropeptidase on RANKL-RANK signalling by cleavage of RANK.FEBS LETTERS,587,(18)
MLA:
Zhao, Yunfeng,et al."Inhibition effect of enteropeptidase on RANKL-RANK signalling by cleavage of RANK".FEBS LETTERS 587..18(2013):2958-2964