A novel function of proteasome

• 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
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 炎症学 / 自己炎症症候群 / 蛋白質 / 生理活性 / プロテオーム / 遺伝子 / プロテアソーム

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
  • NAID: 120006985654
• [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
  • NAID: 10031027542
• [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
  • NAID: 10031027205
• [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
  • NAID: 10030782090
• [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
  • NAID: 10030614950
• [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
  • NAID: 120006985464
• [Journal Article] 遺伝性プロテアソーム機能不全症 (2012)
  • Author(s): 有馬和彦
  • Journal Title: 臨床リウマチ Volume: 24 Pages: 321-323
  • NAID: 130005094911
  • Peer Reviewed
• [Journal Article] 中條―西村症候群の原因遺伝子 (2012)
  • Author(s): 有馬和彦
  • Journal Title: 感染・炎症・免疫 Volume: 42 Pages: 46-49
  • Peer Reviewed
• [Journal Article] 中條―西村症候群の原因遺伝子とプロテアソーム機能異常 (2012)
  • Author(s): 井田弘明、有馬和彦、金澤伸雄、吉浦孝一郎
  • Journal Title: リウマチ科 Volume: 47 Pages: 654-660
  • Peer Reviewed
• [Journal Article] 自己炎症症候群 (2012)
  • Author(s): 川上純、右田清志, 井田弘明, 吉浦孝一郎, 有馬和彦, 江口勝美
  • Journal Title: 日本内科学会雑誌 Volume: 101 Pages: 2733-2739
  • NAID: 10031130670
  • Peer Reviewed
• [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
  • NAID: 10029362129
• [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
  • NAID: 10029362111
• [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
• [Journal Article] Assembly defect due to a PSMB8 mutation reduces proteasome activity and 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, K.
  • Journal Title: Proc.Natl.Acad.Sci.USA Volume: 108 Issue: 36 Pages: 14914-14919
  • DOI: 10.1073/pnas.1106015108
  • Peer Reviewed
• [Journal Article] Nakajo-Nishimura Syndrome (2011)
  • Author(s): 金澤 伸雄 他
  • Journal Title: Japanese Journal of Clinical Immunology Volume: 34 Issue: 5 Pages: 388-400
  • DOI: 10.2177/jsci.34.388
  • NAID: 10029898048
  • ISSN: 0911-4300, 1349-7413
  • Peer Reviewed
• [Journal Article] プロテアソームの機能阻害型遺伝子変異が新規自己炎症疾患である中條-西村症候群を引き起こす (2011)
  • Author(s): 有馬 和彦 他
  • Journal Title: 細胞工学 Volume: 31巻1号 Pages: 68-69
• [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
• [Presentation] Increased expression of inflammatory cytokines in an autoinflammatory disorder, Nakajo-Nishimura syndrome. (2012)
  • Author(s): Arima K
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: Berlin
• [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
• [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
• [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): Kazuhiko Arima et al.
  • Organizer: The Annual European Congress of Rheumatology EULAR 2011
  • Place of Presentation: London, UK
• [Presentation] A novel point mutation causing proteasome dysfunction in NNS (2011)
  • Author(s): Kazuhiko Arima et al.
  • Organizer: The 20th International Rheumatology Symposium
  • Place of Presentation: Kobe, Japan
• [Presentation] Inflammatory cytokines and chemokines in an autoinflammatory disorder, Nakajo-Nishimura syndrome (2011)
  • Author(s): Kazuhiko Arima et al.
  • Organizer: 4th East Asian Group of Rheumatology
  • Place of Presentation: Tokyo, Japan
• [Presentation] 全身性炎症を呈する遺伝性プロテアソーム機能不全症の発見 (2011)
  • Author(s): 有馬 和彦 他
  • Organizer: 第５５回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸、日本
• [Presentation] 中條-西村症候群、全身性炎症を呈する遺伝性プロテアソーム機能不全症 (2011)
  • Author(s): 有馬 和彦 他
  • Organizer: 第３９回日本臨床免疫学会総会(招待講演)
  • Place of Presentation: 東京、日本
• [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/
• [Remarks] Infevers
  • URL: http://fmf.igh.cnrs.fr/ISSAID/infevers/
• [Remarks] 自己炎症症候群情報世界版
  • URL: http://fmf.igh.cnrs.fr/ISSAID/infevers/
• [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。米国生物工学情報センターの運営するメンデル遺伝形式ヒト疾患群電子図書館（NCBI-OMIM）
  • URL: http://omim.org/entry/256040
• [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。