A novel zinc finger protein that inhibits osteoclastogenesis and the function of tumor necrosis factor receptor-associated factor 6.
A variety of surface receptors eliciting diverse cellular responses have been shown to recruit tumor necrosis factor receptor-associated factor (TRAF) adaptor molecules. However, a few TRAF-interacting intracellular proteins that serve as downstream targets or regulators of TRAF function have been identified. In search of new intracellular molecules that bind TRAF6, we carried out a yeast two-hybrid cDNA library screening with an N-terminal segment of TRAF6 as the bait. A novel human C(2)H(2)-type zinc finger family protein was identified, which when coexpressed with TRAF6 led to a suppression of TRAF6-induced activation of NF-kappa B and c-Jun N-terminal kinase. This novel protein was designated TIZ (for TRAF6-inhibitory zinc finger protein). TIZ expression also inhibited the signaling of RANK (receptor activator of NF-kappa B), which together with TRAF6 has been shown to be essential for osteoclastogenesis. Furthermore, the expression level of TIZ appeared to be regulated during the differentiation of human peripheral blood monocytes into osteoclasts. More significantly, transfection of TIZ into the monocyte/macrophage cell line Raw264.7 reduced the RANK ligand-induced osteoclastogenesis of this cell line. Our findings suggest that the novel zinc finger protein TIZ may play a role during osteoclast differentiation by modulating TRAF6 signaling activity.
Shin
Jin Na
JN
National Research Laboratory for Bone Metabolism and School of Dentistry, Chosun University, Gwangju 501-759, Korea.
Kim
Injune
I
Lee
Jung Sup
JS
Koh
Gou Young
GY
Lee
Zang Hee
ZH
Kim
Hong-Hee
HH
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004789:Enzyme Activation; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008156:Luciferases / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6; D013997:Time Factors; D014157:Transcription Factors; D020798:Two-Hybrid System Techniques; D016335:Zinc Fingers
D002352:Carrier Proteins; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011506:Proteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D011993:Recombinant Fusion Proteins; D048029:TNF Receptor-Associated Factor 6; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D014157:Transcription Factors; C451403:ZNF675 protein, human; D008156:Luciferases; D005982:Glutathione Transferase; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases