Research for SUMO-3-involved DNA synthesis induction after X-ray irradiation in human cells

• Project/Area Number: 20510049
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Chiba University
• Principal Investigator: SUGAYA Shigeru Chiba University, 大学院・医学研究院, 助教 (90334177)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: SUMO-2 / 3 / ヒト細胞 / X線 / DNA合成 / NM23-H1 / SUMO-2/3 / siRNA / カドミウム / ストレス応答 / PCNA / 2次元電気泳動 / LC / MS

Research Abstract

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome or basal cell nevus syndrome, is an autosomal dominant disorder that predisposes to both developmental defects and cancer. Fibroblast cells derived from (NBCCS) patients show increased levels of DNA synthesis after X-ray irradiation. We found that the induction of DNA synthesis after irradiation could be caused by the down-regulation of SUMO-3 gene expression in NBCCS cells. Eight hours after X-ray irradiation, an increase in DNA synthesis activity was found in HeLa cells with knockdown of SUMO-2/3. Under these conditions, the expression levels of Nm23-H1, a metastatic suppressor gene, was altered. The decrease of NM23-H1 protein after X-ray irradiation was confirmed by western blot analysis. As expected, treatment of HeLa cells with the siRNA of NM23-H1 resulted in the enhancement of DNA synthesis. These findings suggest that the intimate relationship with the expression of SUMO- SUMO-2/3 and the stability of NM23-H1 after X-ray irradiation, lead to the induction of DNA synthesis.
Nm23-H1 may be modified by SUMO- SUMO-2/3 after X-ray irradiation. The reduction of Nm23-H1 seems to be casually related to the decrease in sumoylation, which in turn, is involved in the induction of DNA synthesis after X-ray irradiation.

Research Products

• [Journal Article] Screening of novel peptide ligands bound to the carboxy-terminal domain of GRP94 by phage display (2011)
  • Author(s): Zahed M., Suzuki T., Kita K., Sugaya S., Suzuki N.
  • Journal Title: Chiba Medical Journal 87 Pages: 61-68
  • NAID: 10030705687
  • Peer Reviewed
• [Journal Article] Studies on the amounts of serum hydroperoxide, MMP-3, urinary 8-OHdG, and salivary IgA in rheumatoid arthritis who experienced Shinrin-yoku (forest-air bathing and walking) (2011)
  • Author(s): Sugaya S., Tanaka K., Akagi T., Kasetani T., Qiu-Ji Z., Guo W-Z., Udagawa A., Sugita K., Ohta R., Suzuki N.
  • Journal Title: Chiba Medical Journal 87 Pages: 5-5
  • Peer Reviewed
• [Journal Article] Anti-proliferative and apoptosis-inducible activity of labdane and abietane diterpenoids from the pulp of Torreya nucifera in HeLa cells (2010)
  • Author(s): Chen S-P., Dong M., Kita K., Shi Q-W., Cong B., Guo W-Z., Sugaya S., Sugita K., Suzuki N.
  • Journal Title: Mol.Med.Rep. 3 Pages: 673-678
  • Peer Reviewed
• [Journal Article] Anti-proliferative and apoptosis-inducible activity of labdane and abietane diterpenoids from the pulp of Torreya nucifera in HeLa cells (2010)
  • Author(s): Chen, S-P., Dong, M., Kita, K., Shi, Q-W., Cong, B., Guo, W-Z., Sueaya, S., Sugita, K., Suzuki, N.
  • Journal Title: Mol.Med.Rep. Volume: 3 Pages: 673-678
  • Peer Reviewed
• [Journal Article] Anti-proliferative and apoptosis-inducible activity of labdane and abietane diterpenoids from the pulp of Torreya nucifera in HeLa cells (2010)
  • Author(s): Chen, S-P., Dong, M., Kita, K., Shi, Q-W., Cong, B., Guo, W-Z., Sugaya, S., Sugita, K., Suzuki, N.
  • Journal Title: Mol.Med.Rep. (In press)
  • Peer Reviewed
• [Journal Article] Anti-proliferative and apoptosis-inducible activity of Sarcodonin G from Sarcodon scabrosus in HeLa cells (2009)
  • Author(s): Dong M., Chen S.P., Kita K., Ichimura Y., Guo W-Z., Lu S., Sugaya S., Hiwasa T., Takiguchi M., Mori N., Kashima A., Morimura K., Hirota M., Suzuki N.
  • Journal Title: Int.J.Oncol. 34 Pages: 201-207
  • Peer Reviewed
• [Journal Article] Nm23-H1 is responsible for SUMO-2-involved DNA synthesis induction after X-ray irradiation in human cells (2009)
  • Author(s): Guo W., Sugaya S., Satoh M., Tomonaga T., Nomura F., Hiwasa T., Kita K., Takiguchi M., Suzuki N.
  • Journal Title: Archives of Biochemistry and Biophysics 486 Pages: 81-87
  • Peer Reviewed
• [Journal Article] Nm23-H1 is responsible for SUMO-2-involved DNA synthesis induction after X-ray irradiation in human cells (2009)
  • Author(s): Guo, W., Sugaya S., Satoh M., Tomonaga T., Nomura F., Hiwasa T, Takiguchi M., Kita K., Suzuki N.
  • Journal Title: Arch.Biochem.Biophys. 486 Pages: 81-87
  • Peer Reviewed
• [Journal Article] Anti-proliferative and apoptosis-inducible activity of Sarcodonin G from Sarcodon scabrosus in HeLa cells (2009)
  • Author(s): Dong M., Chen S., Kita K., Ichimura Y., Guo W., Lu S., Sugaya S., Hiwasa T., Takiguchi M., Mori N., Kashima A., Morimura K., Hirota M., Suzuki N
  • Journal Title: Int.J.Oncol. 34 Pages: 201-207
  • Peer Reviewed
• [Journal Article] Anti-proliferative and apoptosis-inducible activity of Sarcodonin G from Sarcodon scabrosus in Hela cells (2009)
  • Author(s): Dong M., Chen S., Kita K., Ichimura Y., Guo W., Lu S., Sugaya S., Hiwasa T., Takiguchi M., Mori N., Kashima A., Morimura K., Hirota M., Suzuki N
  • Journal Title: Int.J.Oncol 34 Pages: 201-207
  • Peer Reviewed
• [Journal Article] Nm-23Hl is responsible for SUMO-2-involved DNA synthesis induction after X-ray irradiation in human cells (2009)
  • Author(s): Guo, W., Sugaya S., Satoh M., Tomonaga T., Nomura F., Hiwasa t., Takiguchi M., Kita K., Suzuki N.
  • Journal Title: Arch.Biochem.Biophys.
  • Peer Reviewed
• [Journal Article] a novel HSP27-interacted protein, is involved in resistance to UVC-induced cell death in human APr-1 cells (2008)
  • Author(s): Tong X., Kita K., Karata K., Zhu C., Sugaya S., Ichimura Y., Satoh M., Tomonaga T., Nomura F., Jin Y., Suzuki N. Annexin II
  • Journal Title: Photochem.Photobiol. 84 Pages: 1455-1461
  • Peer Reviewed
• [Journal Article] Discrepancy of Cadmium Susceptibility Between Human RSa Cells and Variant UVr-1 Cells (2008)
  • Author(s): Ji Z-q., Sugaya S., Suzuki N.
  • Journal Title: Chiba Med.J. 84 Pages: 75-82
  • NAID: 10026993502
  • Peer Reviewed
• [Journal Article] Down-regulation of Molecular Chaperone GRP78/Bip Expression Involved in Enhancement of Human RS Cell Mutability (2008)
  • Author(s): Hirano J., Kita K., Sugaya S., Ichimura Y., Yamamori H., Nakajima N., Suzuki N.
  • Journal Title: Pancreas 36
  • Peer Reviewed
• [Journal Article] Down-regulation of Molecuiar Chaperone GRP78/Bip Expression In volved in Enhancement of Human RS Cell Mutability. (2008)
  • Author(s): Hirano J., Kita K., Sugaya S., Ichimura Y., Yamamori H., Nakajima N., Suzuki, N.
  • Journal Title: Pancreas 36
  • Peer Reviewed
• [Journal Article] Annexin II, a novel HSP27-interacted protein, is involved in resistance to UVC-induced cell death in human Apr-l cells. (2008)
  • Author(s): Tong, X., Kita, K., Karata, K., Zhu, C., Sugaya, S., Ichimura Y., Satoh, M., Tomonaga, T., Nomura, F., Jin, Y., Suzuki, N.
  • Journal Title: Photochem.Photobiol 34 Pages: 1455-1461
  • Peer Reviewed
• [Journal Article] Discrepancy of Cadmium Susceptility Between Human RSa Cells and Variant Uvr-l Cells (2008)
  • Author(s): Ji, Z., Sugaya S, Suzuki, N.
  • Journal Title: Chiba Medical Journal 84 Pages: 75-82
  • Peer Reviewed
• [Journal Article] Screening of novel peptide ligands bound to the carboxy-termingl domain of GRP94 by phage display
  • Author(s): Zahed M., Suzuki T., Kita K. Sugaya S., Suzuki N.
  • Journal Title: Chiba Medical Journal Volume: in press
  • Peer Reviewed
• [Journal Article] Studies on the amounts of serum hydroperoxide, MMP-3, urinary 8-OHdG, and salivary IgA in rheumatoid arthritis patients who experienced Shinrin-yoku(forest-air bathing and walking)
  • Author(s): Sueava, S., Tanaka K., Akagi T., Kasetani T., Qiu-Ji Z., Guo WZ., Udagawa A., Nomura J., Sugita K., Ohta R., Suzuki N.
  • Journal Title: Chiba Medical Journal Volume: in press
  • Peer Reviewed
• [Presentation] カドミウムによるヒト細胞増殖阻害に関わるユビキチン様タンパクSUMO-2/3 (2010)
  • Author(s): 菅谷茂、古川聡子、喜多和子、田中健史、紀仲秋、鈴木信夫
  • Organizer: 第83回日本生化学会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] 腫瘍転移抑制因子NM23-H1は、ユビキチン様タンパクSUMO-2を介したX線照射後のDNA合成能の増大に関わる (2010)
  • Author(s): 菅谷茂、郭文智、佐藤守、朝長毅、野村文夫、日和佐隆樹、瀧口正樹、喜多和子、鈴木信夫
  • Organizer: 第7回千葉プロテオミクス研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-11-13
• [Presentation] カドミウムによるヒト細胞増殖阻害に関わるユビキチン様タンパクSUMO-2/3 (2010)
  • Author(s): 菅谷茂、古川聡子、喜多和子、田中健史、紀仲秋、鈴木信夫
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド(神戸市中央区)
• [Presentation] 細胞外に添加されたHSPB-Aによるコケイン症候群患者由来細胞の紫外線致死抵抗化 (2010)
  • Author(s): 喜多和子、杉田克生、陳仕萍、佐藤哲生、郭文智、鈴木敏和、菅谷茂、鈴木信夫
  • Organizer: 日本放射線影響学会第53回大会
  • Place of Presentation: 京都
• [Presentation] ユビキチン様タンパクSUMO-2/3のヒト細胞で見られるX線照射後のDNA合成能の増大に関わる役割 (2009)
  • Author(s): 郭文智、菅谷茂、佐藤守、朝長毅、野村文夫、鈴木信夫
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州(小倉)
• [Presentation] ヒト細胞の紫外線致死抵抗化に関わるタンパク質annexin IIとその代謝を調節するHSP27 (2009)
  • Author(s): 陳仕萍、喜多和子、金元虎、〓暁波、菅谷茂、鈴木敏和、鈴木信夫
  • Organizer: 日本放射線影響学会第52回大会
  • Place of Presentation: 広島
• [Presentation] ユビキチン様タンパクSUMO-2を介したX線照射後のDNA合成能の増大に関わる腫瘍転移抑制因子NM23-H1の発見 (2009)
  • Author(s): 菅谷茂、郭文智、佐藤守、朝長毅、野村文夫、日和佐隆樹、瀧口正樹、喜多和子、鈴木信夫
  • Organizer: 日本放射線影響学会第52回大会
  • Place of Presentation: 広島
• [Presentation] ユビキチン様タンパク質SUM0-2/3のヒト細胞で見られるX線照射後のDNA合成能の増大に関わる役割 (2008)
  • Author(s): 郭文智、菅谷茂、佐藤守、朝長毅、野村文夫、鈴木信夫
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州(小倉)
• [Book] 千葉学ブックレット-千葉の健康2 (2011)
  • Author(s): 鈴木信夫、菅谷茂
  • Total Pages: 89
  • Publisher: 千葉日報社
• [Remarks] ホームページ情報(研究成果データベース)Gorlin症候群の病態解明と治療法確立のための臨床的研究班
  • URL: http://www.nanbyou.or.jp/kenkyuhan/syoreimeibo2010/syorei171.htm
• [Remarks] 日中医学協会報告
• [Patent(Industrial Property Rights)] 紫外線防止剤 (2008)
  • Inventor(s): 鈴木信夫、戸村真澄、伊藤晴夫、菅谷茂、喜多和子、呂颯
  • Industrial Property Rights Holder: 国立大学法人千葉大学、株式会社I&C、伊藤晴夫
  • Filing Date: 2008-12-24
• [Patent(Industrial Property Rights)] 紫外線防止剤 (2008)
  • Inventor(s): 鈴木信夫、戸村真澄、伊藤晴夫、菅谷茂、喜多和子、ロサ
  • Industrial Property Rights Holder: 千葉大学、株式会社I&C、伊藤晴夫
  • Filing Date: 2008-12-24