NLRP6 facilitates the interaction between TAB2/3 and TRIM38 in rheumatoid arthritis fibroblast-like synoviocytes.

Abstract

In the present study, we investigated the role of nucleotide oligomerization domain-like receptor family pyrin domain containing 6 (NLRP6) in rheumatoid arthritis (RA) and explored the underlying mechanism. We found that both mRNA and protein levels of NLRP6 are attenuated in synovial tissues and fibroblast-like synoviocytes (FLS) of RA patients compared to patients with osteoarthritis. We also observed that pro-inflammatory cytokine production is decreased and nuclear factor-kappa B activation is inhibited in NLRP6-overexpressing RA-FLS. Furthermore, we found that NLRP6 overexpression promotes transforming growth factor-b-activated kinase 1-binding protein 2/3 lysosome-dependent degradation, and we provide evidence showing that NLRP6 plays the role of providing the docking site to facilitate the interaction between transforming growth factor-b-activated kinase 1-binding protein 2/3 and tripartite motif 38 in RA-FLS.

• Authors: Yang Lin, Zhengqiang Luo
• Journal: FEBS letters (FEBS Lett) Vol. 591 Issue 8 Pg. 1141-1149 (04 2017) ISSN: 1873-3468 [Electronic] England
• PMID: 28295271 (Publication Type: Comparative Study, Journal Article)
• Copyright: © 2017 Federation of European Biochemical Societies.

Chemical References

• Adaptor Proteins, Signal Transducing
• Carrier Proteins
• IL1B protein, human
• IL6 protein, human
• Interleukin-1beta
• Interleukin-6
• Intracellular Signaling Peptides and Proteins
• NLRP6 protein, human
• RNA, Messenger
• Recombinant Proteins
• TAB2 protein, human
• TAB3 protein, human
• TNF protein, human
• Tripartite Motif Proteins
• Tumor Necrosis Factor-alpha
• TRIM38 protein, human
• Ubiquitin-Protein Ligases

Topics

• Adaptor Proteins, Signal Transducing (chemistry, metabolism)
• Arthritis, Rheumatoid (immunology, metabolism, pathology)
• Carrier Proteins (chemistry, metabolism)
• Cells, Cultured
• Down-Regulation
• Genes, Reporter
• Humans
• Immunoprecipitation
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• Intracellular Signaling Peptides and Proteins (antagonists & inhibitors, chemistry, genetics, metabolism)
• Osteoarthritis (immunology, metabolism, pathology)
• Protein Interaction Domains and Motifs
• RNA Interference
• RNA, Messenger (metabolism)
• Recombinant Proteins (chemistry, metabolism)
• Synovial Membrane (immunology, metabolism, pathology)
• Synoviocytes (immunology, metabolism, pathology)
• Tripartite Motif Proteins
• Tumor Necrosis Factor-alpha (metabolism)
• Ubiquitin-Protein Ligases