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Published on: March 18, 2019

A novel zinc finger protein that inhibits osteoclastogenesis and the function of tumor necrosis factor

Jin Na Shin1, Injune Kim, Jung Sup Lee

  • 1National Research Laboratory for Bone Metabolism and School of Dentistry, Chosun University, Gwangju 501-759, Korea.

The Journal of Biological Chemistry
|December 26, 2001
PubMed

Insights

Researchers discovered TIZ, a novel zinc finger protein that inhibits TRAF6 signaling. TIZ plays a role in osteoclast differentiation by modulating this pathway, impacting bone cell formation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Immunology

Background:

  • Tumor necrosis factor receptor-associated factors (TRAFs) are key adaptor molecules in cellular signaling pathways.
  • Identifying TRAF-interacting proteins is crucial for understanding downstream cellular responses.
  • Limited intracellular proteins regulating TRAF function have been identified.

Purpose of the Study:

  • To identify novel intracellular proteins that interact with TRAF6.
  • To investigate the functional role of a newly identified TRAF6-binding protein in cellular signaling and osteoclastogenesis.

Main Methods:

  • Yeast two-hybrid cDNA library screening using a TRAF6 N-terminal segment as bait.
  • Coexpression assays to assess the effect of the novel protein on TRAF6-induced signaling.
  • Analysis of RANK signaling and osteoclast differentiation in cell lines.

Main Results:

  • A novel human C(2)H(2)-type zinc finger protein, designated TIZ (TRAF6-inhibitory zinc finger protein), was identified.
  • TIZ suppressed TRAF6-induced activation of NF-kappa B and c-Jun N-terminal kinase.
  • TIZ inhibited RANK signaling and reduced RANK ligand-induced osteoclastogenesis in Raw264.7 cells, with its expression regulated during monocyte differentiation into osteoclasts.

Conclusions:

  • The novel zinc finger protein TIZ modulates TRAF6 signaling activity.
  • TIZ plays a significant role in regulating osteoclast differentiation.
  • TIZ represents a potential therapeutic target for conditions involving osteoclast activity.

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