Inhibitory effects of ubiquitination of synoviolin by PADI4
| Autor: | Yukari Okubo, Toshihiro Nakajima, Satoko Aratani, Naoko Yagishita, Kusuki Nishioka, Yoshihisa Yamano, Hidetoshi Fujita |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Cancer Research Ubiquitin-Protein Ligases medicine.medical_treatment Gene Expression medicine.disease_cause Biochemistry Protein citrullination Autoimmunity Arthritis Rheumatoid 03 medical and health sciences Protein-Arginine Deiminase Type 4 Ubiquitin Genetics medicine Humans Protein Interaction Domains and Motifs Molecular Biology biology Ubiquitination Citrullination Synoviocytes Ubiquitin ligase 030104 developmental biology Cytokine Oncology Protein-Arginine Deiminases biology.protein Cancer research Unfolded protein response Molecular Medicine Signal transduction Protein Binding |
| Zdroj: | Molecular Medicine Reports. 16:9203-9209 |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2017.7764 |
| Popis: | Rheumatoid arthritis (RA) is a chronic inflammatory articular disease that is characterized by synovial hyperplasia. A number of signaling pathways are associated with the development and induced symptoms of RA. Notably, patients with RA have increased protein citrullination and generation of auto‑antibodies against citrullinated proteins. Genome wide association studies have revealed that peptidyl‑arginine deiminase 4 (PADI4) is an enzyme implicated in citrullination in the RA synovium. Autoantibodies targeting citrullinated proteins are used as diagnostic markers in patients with RA. The functions associated with citrullinated proteins are thought to induce autoimmunity, however, the regulatory mechanisms of citrullination via PADI4 are unclear. The group has previously cloned an E3 ubiquitin ligase, synoviolin (SYVN1), from the RA synovium, demonstrating that SYVN1 serves critical roles in synovial hyperplasia. The data indicated that the endoplasmic reticulum (ER) associated degradation system, which involves SYVN1, may have important roles in the proliferation of synoviocytes. In addition, ubiquitination by SYVN1 is associated with fibrosis, inflammation and cytokine production via the regulation of ER stress signals and quality control of proteins. The present study investigated the crosstalk between the representative post‑translational signaling processes, citrullination and ubiquitination. The results revealed that PADI4 interacted with SYVN1 directly and that overexpression of PADI4 suppressed the ubiquitination of proteins. Thus, a reduction in ER stress induced by PADI4 may abrogate the initiation of chronic RA by suppressing the proliferative signals of RA synoviocytes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|