A novel function of proteasome

2012 Fiscal Year Final Research Report

• Project/Area Number: 23791115
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Nagasaki University
• Principal Investigator: ARIMA Kazuhiko 長崎大学, 医歯薬学総合研究科, 助教 (30423635)
• Project Period (FY): 2011 – 2012
• Keywords: 炎症学 / 自己炎症症候群

Research Abstract

The ubiquitin-proteasome pathway is responsible for selective degradation of short-lived, misfolded and toxic proteins. It plays an important rule in tuning the intracellular environment.Nakajo-Nishimura syndrome (NNS) (MIM 256040) is an autoinflammatory disorder with impaired proteasome function, its newly identified causative mutation and inflammatory symptoms including periodic fever and skin rash.Our findings suggest that decrease of proteasome activity is associated with an increased expression of inflammatory cytokines. The ubiquitin-proteasome pathway would play an important rule against inflammation. This may provide a new insight into the pathogenesis of other persistent inflammatory diseases.

Research Products

• [Journal Article] Branched-chain amino acid deficiency stabilizes insulin-induced vascular endothelial growth factor mRNA in hepatocellular carcinoma cells (2012)
  • Author(s): Miuma S, Ichikawa T, Arima K, Takeshita S, Muraoka T, Matsuzaki T, Ootani M, Shibata H, Akiyama M, Ozawa E, Miyaaki H, Taura N, Takeshima F, Nakao K
  • Journal Title: J Cell Biochem Volume: 113(10) Pages: 3113-21
• [Journal Article] Prophylactic and therapeutic efficacies of a selective inhibitor of the immunoproteasome for Hashimoto's thyroiditis, but not for Graves' hyperthyroidism, in mice (2012)
  • Author(s): Nagayama Y, Nakahara M, Shimamura M, Horie I, Arima K, Abiru N
  • Journal Title: Clin Exp Immunol Volume: 168(3) Pages: 268-73
• [Journal Article] The diagnostic utility of anti-melanoma differentiation-associated gene 5 antibody testing for predicting the prognosis of Japanese patients with DM (2012)
  • Author(s): Koga T, Fujikawa K, Horai Y, Okada A, Kawashiri SY, Iwamoto N, Suzuki T, Nakashima Y, Tamai M, Arima K, Yamasaki S, Nakamura H, Origuchi T, Hamaguchi Y, Fujimoto M, Ishimatsu Y, Mukae H, Kuwana M, Kohno S, Eguchi K, Aoyagi K, Kawakami A
  • Journal Title: Rheumatology (Oxford) Volume: 51(7) Pages: 1278-84
• [Journal Article] Magnetic resonance imaging (MRI) detection of synovitis and bone lesions of the wrists and finger joints in early-stage rheumatoid arthritis: comparison of the accuracy of plain MRI-based findings and gadolinium-diethylenetriamine pentaacetic acid-enhanced MRI-based findings (2012)
  • Author(s): Tamai M, Kawakami A, Uetani M, Fukushima A, Arima K, Fujikawa K, Iwamoto N, Aramaki T, Kamachi M, Nakamura H, Ida H, Origuchi T, Aoyagi K, Eguchi K
  • Journal Title: Mod Rheumatol Volume: 22(5) Pages: 654-8
• [Journal Article] High serum matrix metalloproteinase 3 is characteristic of patients with paraneoplastic remitting seronegative symmetrical synovitis with pitting edema syndrome (2012)
  • Author(s): Origuchi T, Arima K, Kawashiri SY, Tamai M, Yamasaki S, Nakamura H, Tsukada T, Aramaki T, Furuyama M, Miyashita T, Kawabe Y, Iwanaga N, Terada K, Ueki Y, Fukuda T, Eguchi K, Kawakami A
  • Journal Title: Mod Rheumatol Volume: 22(4) Pages: 584-8
• [Journal Article] Treatment discontinuation in patients with very early rheumatoid arthritis in sustained simplified disease activity index remission after synthetic disease-modifying anti-rheumatic drug administration (2012)
  • Author(s): Kita J, Tamai M, Arima K, Nakashima Y, Suzuki T, Kawashiri SY, Iwamoto N, Okada A, Koga T, Yamasaki S, Nakamura H, Origuchi T, Ida H, Aoyagi K, Uetani M, Eguchi K, Kawakami A
  • Journal Title: Mod Rheumatol Volume: 22(3) Pages: 346-52
• [Journal Article] Delayed treatment with tumor necrosis factor inhibitors in incomplete responders to synthetic disease-modifying anti-rheumatic drugs shows an excellent effect in patients with very early rheumatoid arthritis with poor prognosis factors (2012)
  • Author(s): Kita J, Tamai M, Arima K, Nakashima Y, Suzuki T, Kawashiri SY, Okada A, Koga T, Yamasaki S, Nakamura H, Origuchi T, Aramaki T, Nakashima M, Fujikawa K, Tsukada T, Ida H, Aoyagi K, Uetani M, Eguchi K, Kawakami A
  • Journal Title: Mod Rheumatol Volume: 22(2) Pages: 195-201
• [Journal Article] Long-term follow-up of adalimumab monotherapy for rheumatoid arthritis in Japanese patients: a report of six cases (2012)
  • Author(s): Ichinose K, Origuchi T, Kawashiri SY, Iwamoto N, Fujikawa K, Aramaki T, Kamachi M, Arima K, Tamai M, Nakamura H, Ida H, Kawakami A, Eguchi K
  • Journal Title: Rheumatol Int Volume: 32 Pages: 483-7
• [Journal Article] Proteasome assembly defect due to a proteasome subunit beta type 8 (PSMB8) mutation causes the autoinflammatory disorder, Nakajo-Nishimura syndrome (2011)
  • Author(s): Arima K, Kinoshita A, Mishima H, Kanazawa N, Kaneko T, Mizushima T, Ichinose K, Nakamura H, Tsujino A, Kawakami A, Matsunaka M, Kasagi S, Kawano S, Kumagai S, Ohmura K, Mimori T, Hirano M, Ueno S, Tanaka K, Tanaka M, Toyoshima I, Sugino H, Yamakawa A, Tanaka K, Niikawa N, Furukawa F, Murata S, Eguchi K, Ida H, Yoshiura KI
  • Journal Title: Proc Natl Acad Sci U S A Volume: 108 Pages: 14914-9
• [Journal Article] Reduction in serum levels of substance P in patients with rheumatoid arthritis by etanercept, a tumor necrosis factor inhibitor (2011)
  • Author(s): Origuchi T, Iwamoto N, Kawashiri SY, Fujikawa K, Aramaki T, Tamai M, Arima K, Nakamura H, Yamasaki S, Ida H, Kawakami A, Ueki Y, Matsuoka N, Nakashima M, Mizokami A, Kawabe Y, Mine M, Fukuda T, Eguchi K
  • Journal Title: Mod Rheumatol Volume: 21 Pages: 244-50
• [Journal Article] Contribution of an adenine to guanine single nucleotide polymorphism of the matrix metalloproteinase-13 (MMP-13) -77 promoter region to the production of anticyclic citrullinated peptide antibodies in patients with HLA-DRB1*shared epitope-negative rheumatoid arthritis (2011)
  • Author(s): Iwamoto N, Kawakami A, Arima K, Tamai M, Nakamura H, Kawashiri SY, Kita J, Okada A, Koga T, Kamachi M, Yamasaki S, Ichinose K, Ida H, Origuchi T, Eguchi K
  • Journal Title: Mod Rheumatol Volume: 21 Pages: 240-3
• [Journal Article] Post-transcriptional regulation of IL-6 production by Zc3h12a in fibroblast-like synovial cells (2011)
  • Author(s): Koga T, Yamasaki S, Migita K, Kita J, Okada A, Kawashiri S, Iwamoto N, Tamai M, Arima K, Origuchi T, Nakamura H, Osaki M, Tsurumoto T, Shindo H, Eguchi K, Kawakami A
  • Journal Title: Clin Exp Rheumatol Volume: 29(6) Pages: 906-12
• [Presentation] Increased expression of inflammatory cytokines in an autoinflammatory disorder, Nakajo-Nishimura syndrome (2012)
  • Author(s): K Arima, N Kanazawa, F Furukawa, H Ida, K Yoshiura
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: Berlin, Germany
  • Year and Date: 20120000
• [Presentation] Nakajo-Nishimura syndrome (NNS) is a systemic inflammatory disorder that segregates in an autosomal recessive fashion (2011)
  • Author(s): Arima K, Hiroaki Ida, Tomoki Origuchi, Nobuo Kanazawa, Katsumi Eguchi
  • Organizer: The 20th International Rheumatology Symposium Kobe
  • Place of Presentation: Japan
  • Year and Date: 20110000
• [Presentation] Decrease of proteasome activity is associated with a novel mutation of the proteasome catalytic subunit in an autoinflammatory disorder, Nakajo-Nishimura syndrome (2011)
  • Author(s): Arima K, Kanazawa N, Mishima H, Kinoshita A, Ida H, Murata S, Yoshiura K, Eguchi K
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: London UK
  • Year and Date: 20110000
• [Remarks] に我々の研究成果である遺伝子変異の登録分野が新しく作成されている
  • URL: http://fmf.igh.cnrs.fr/ISSAID/infevers/