Cited by 200Bone Metabolism and DiseasesCell death mechanisms and regulationCytokine Signaling Pathways and Interactions

Characterization of Structural Domains of Human Osteoclastogenesis Inhibitory Factor

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Yamaguchi, Kyoji, Kinosaki, Masahiko, Goto, Masaaki, Kobayashi, Fumie, Tsuda, Eisuke, Morinaga, Tomonori, Higashio, Kanji·1998·Journal of Biological Chemistry

Abstract

Osteoclastogenesis inhibitory factor (OCIF) is a heparin-binding secretory glycoprotein that belongs to the tumor necrosis factor receptor (TNFR) family. OCIF is present both as a approximately 60-kDa monomer and a disulfide-linked homodimer. We attempted to characterize the seven structural domains of OCIF by determining the capabilities of various OCIF mutants to inhibit osteoclastogenesis, to interact with heparin, and to form dimers. We also examined a potential of domains 5 and 6, death domain homologous regions (DDHs), for inducing cell death by expressing OCIF/Fas fusion proteins. Our results show that: (i) the N-terminal portion of OCIF containing domains 1-4, which have structural similarity to the extracellular domains of the TNFR family proteins, is sufficient to inhibit osteoclastogenesis; (ii) a heparin-binding site is located in domain 7, and affinity for heparin does not correlate with the inhibitory activity; (iii) Cys-400 in domain 7 is the residue responsible for dimer formation; and (iv) the C-terminal portion containing domains 5 and 6, DDHs, has a high potential for mediating a cytotoxic signal when it is expressed in cells as an OCIF/Fas fusion protein in which the transmembrane region of Fas is inserted in front of DDHs.

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Crossref · 10.1074/jbc.273.9.5117

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Authors
Yamaguchi, K., Kinosaki, M., Goto, M., Kobayashi, F., Tsuda, E., Morinaga, T., & Higashio, K.
Affiliations
Megmilk Snow Brand (Japan) (JP)
Corresponding author
Yamaguchi, Kyoji
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1998-02
Volume
273
Issue
9
Pages
5117-5123
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2043992170
Cited by
200
References
26
Citations by year
2026: 3 · 2025: 2 · 2024: 2 · 2022: 3 · 2020: 6 · 2019: 5 · 2018: 7 · 2017: 7 · 2016: 5 · 2015: 7 · 2014: 7 · 2013: 7 · 2012: 9
FWCI
5.19
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
osteoprotegerin, osteoclastogenesis inhibition, TNF receptor superfamily, heparin binding, protein domain structure, homodimerization, secretory glycoproteins
MeSH terms
Cytotoxicity, Immunologic, Dose-Response Relationship, Drug, Genetic Vectors, Glycoproteins, Growth Inhibitors, Heparin, Humans, Mutation, Osteoclasts, Protein Binding, Recombinant Fusion Proteins, Structure-Activity Relationship, Signal Transduction, Apoptosis, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, fas Receptor, Dimerization, Osteoprotegerin

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