Roles of 53BP1 in elimination of an apoptotic cell

• Project/Area Number: 24651056
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kanazawa Medical University
• Principal Investigator: IWABUCHI Kuniyoshi 金沢医科大学, 医学部, 教授 (10232696)
• Co-Investigator(Renkei-kenkyūsha): NAKAMURA Akira 金沢医科大学, 医学部, 教授 (20344723) ; SUNATANI Yumi 金沢医科大学, 医学部, 助教 (70581057)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: アポトーシス / ヒストン / DNA / 53BP1 / p53 / スタウロスポリン / ヌクレオソーム / 自己抗体 / 細胞膜 / 分子生物学

Research Abstract

p53 binding protein-1(53BP1) accumulates at sites of DNA double-strand breaks, where it suppresses DNA end resection, and facilitates repair of DNA double-strand breaks by non-homologous end joining. In this study, we found that in apoptotic cells 53BP1 is cleaved to generate a fragment of 53BP1 in a caspase-dependent manner. This 53BP1 fragment is localized on the surface of apoptotic cells. Our data suggest that 53BP1 regulates clearance of apoptotic cells by a macrophage.

Research Products

• [Journal Article] DHX36 enhances RIG-I signaling by facilitating PKR-mediated antiviral stress granule formation (2014)
  • Author(s): Yoo JS, Takahasi K, Ng CS, Ouda R, Onomoto K, Yoneyama M, Lai JC, Lattmann S, Nagamine Y, Matsui T, Iwabuchi K, Kato H, Fujita T
  • Journal Title: PLoS Pathog Volume: 10(3)
  • NAID: 120005466661
  • Peer Reviewed
• [Journal Article] RNA binding protein RBM8A (Y14) and MAGOH localize to centrosome in human A549 cells (2014)
  • Author(s): Ishigaki Y, Nakamura Y, Tatsuno T, Hashimoto M, Iwabuchi K, Tomosugi N
  • Journal Title: Histochem Cell Biol Volume: 141(1) Pages: 101-109
  • Peer Reviewed
• [Journal Article] DHX36 Enhances RIG-I Signaling by Facilitating PKR-Mediated Antiviral Stress Granule Formation (2014)
  • Author(s): Yoo, J-S., Takahasi, K., Ng, CS., Ouda, R., Onomoto, K., Yoneyama, M., Lai, J-C., Lattmann, S., Nagamine, Y., Matsui, T., Iwabuchi, K., Kato, H. Fujita, T.
  • Journal Title: PLoS Pathog Volume: 10(3) Issue: 3 Pages: 1-18
  • DOI: 10.1371/journal.ppat.1004012
  • NAID: 120005466661
  • Peer Reviewed / Open Access
• [Journal Article] Protein kinase CK2 is required for the recruitment of 53BP1 to sites of DNA double-strand break induced by radiomimetic drugs. (2014)
  • Author(s): Guerra B, Iwabuchi K, Issinger OG.
  • Journal Title: Cancer Lett Volume: 345 Issue: 1 Pages: 115-123
  • DOI: 10.1016/j.canlet.2013.11.008
  • Peer Reviewed
• [Journal Article] RNA binding protein RBM8A (Y14) and MAGOH localize to centrosome in human A549. (2014)
  • Author(s): Ishigaki Y, Nakamura Y, Tatsuno T, Hashimoto M, Iwabuchi K, Tomosugi N.
  • Journal Title: Histochem Cell Biol Volume: 141 Issue: 1 Pages: 101-109
  • DOI: 10.1007/s00418-013-1135-4
  • Peer Reviewed
• [Journal Article] DNA Ligase IV and Artemis act cooperatively to suppress homologous recombination in human cells : Implications for DNA double-strand break repair (2013)
  • Author(s): Kurosawa A, Saito S, So S, Hashimoto M, Iwabuchi K, Watabe H, Adachi N
  • Journal Title: PLoS One Volume: 8
  • Peer Reviewed
• [Journal Article] Depletion of RNA-binding protein RBM8A (Y14) causes cell cycle deficiency and apoptosis in human cells (2013)
  • Author(s): Ishigaki Y, Nakamura Y, Tatsuno T, Hashimoto M, Shimasaki T, Iwabuchi K, Tomosugi N
  • Journal Title: Exp Biol Med Volume: 238(8) Pages: 889-897
  • Peer Reviewed
• [Journal Article] Sensitive immunodetection of radiotoxicity after iodine-131 therapy for thyroid cancer usingγ-H2AX foci of DNA damage in lymphocytes (2013)
  • Author(s): Doai M, Watanabe N, Takahashi T, Taniguchi M, Tonami H, Iwabuchi K, Kayano D, Fukuoka M, Kinuya S
  • Journal Title: Ann Nucl Med Volume: 27 Pages: 233-238
  • Peer Reviewed
• [Journal Article] Depletion of RNA-binding protein RBM8A (Y14) causes cell cycle deficiency and apoptosis in human cells. (2013)
  • Author(s): Ishigaki Y, Nakamura Y, Tatsuno T, Hashimoto M, Shimasaki T, Iwabuchi K, Tomosugi N.
  • Journal Title: Exp Biol Med Volume: 238 Issue: 8 Pages: 889-897
  • DOI: 10.1177/1535370213494646
  • Peer Reviewed
• [Journal Article] DNA Ligase IV and Artemis Act Cooperatively to Suppress Homologous Recombination in Human Cells: Implications for DNA Double-Strand Break Repair. (2013)
  • Author(s): Kurosawa A, Saito S, So S, Hashimoto M, Iwabuchi K, Watabe H, Adachi N.
  • Journal Title: PLoS One Volume: 8 Issue: 8 Pages: e72253-e72253
  • DOI: 10.1371/journal.pone.0072253
  • Peer Reviewed
• [Journal Article] Sensitive immunodetection of radiotoxicity after iodine-131 therapy for thyroid cancer using γ-H2AX foci of DNA damage in lymphocytes (2013)
  • Author(s): Doai M
  • Journal Title: Annals of Nuclear Medicine Volume: 27 Issue: 3 Pages: 233-238
  • DOI: 10.1007/s12149-012-0678-0
  • Peer Reviewed
• [Journal Article] Knockdown of stromal interaction molecule 1 (STIM1) suppresses store-operated calcium entry, cell proliferation and tumorigenicity in human epidermoid carcinoma A431 cells (2012)
  • Author(s): Yoshida J, Iwabuchi K, Matsui T, Ishibashi T, Masuoka T, Nishio M
  • Journal Title: Biochem Pharmacol Volume: 84 Pages: 1592-1603
  • Peer Reviewed
• [Journal Article] Knockdown of stromal interaction molecule 1 (STIM1) suppresses store-operated calcium entry, cell proliferation and tumorigenicity in human epidermoid carcinoma A431 cells. (2012)
  • Author(s): Jyunko Yoshida
  • Journal Title: Biochem Pharmacol. Volume: 84 Issue: 12 Pages: 1592-1603
  • DOI: 10.1016/j.bcp.2012.09.021
  • Peer Reviewed
• [Presentation] 53BP1によるp53機能の制御 (2013)
  • Author(s): 松井理、砂谷優実、逆井良、橋本光正、岩淵邦芳
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: 青森
• [Presentation] カスパーゼによるXRCC4切断とXRCC4によるCADの核内移行促進機構の解明 (2013)
  • Author(s): 砂谷優実、Kamdar R.P.、Sharma M. K.、松井理、逆井良、橋本光正、松本義久、岩淵邦芳
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: 青森
• [Presentation] Calcium sensor STIM1 plays an essential role in human epidermoid carcinoma cell growth, migration, and tumorigenicity (2013)
  • Author(s): Yoshida J, Iwabuchi K
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Scilencing of calcium sensor protein stromal interoctionmolecule 1 (STIM1) suppresses cell proliferation and tumorigenicity in human epidermoid carcinoma A431 cells (2013)
  • Author(s): Yoshida J, Iwabuchi K, Ishibashi T, Masuoka T, Nishio M
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡
• [Presentation] Calcium sensor STIM1 plays an essential role in human epidermoid carcinoma cell growth, migration, and tumorigenicity. (2013)
  • Author(s): 吉田純子, 岩淵邦芳
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜（パシフィコ横浜）
• [Presentation] カスパーゼによるXRCC4切断とXRCC4によるCADの核内移行促進機構の解明 (2013)
  • Author(s): 砂谷 優実, カムダール ラディカ パンカジ, シャルマ ムケシュ クマール, 松井 理, 逆井 良, 橋本 光正, 松本 義久, 岩淵 邦芳
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: 青森（ホテルクラウンパレス青森）
• [Presentation] 53BP1によるp53機能の制御 (2013)
  • Author(s): 松井 理, 砂谷 優実, 逆井 良, 橋本 光正, 岩淵 邦芳
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: 青森（ホテルクラウンパレス青森）
• [Presentation] Radiotoxicity after radioisotope therapy for bone metastases using gammma-H2AX foci of DNA damage in lymphocytes (2013)
  • Author(s): Mariko Doai
  • Organizer: SNMMI 60th Annual Meeting
  • Place of Presentation: Vancouver, BC, Canada
• [Presentation] DNA二本鎖切断修復タンパク質XRCC4を介したアポトーシス制御機構の解明 (2012)
  • Author(s): 橋本優実、Kamdar R.P.、Sharma M. K.、松井理、橋本光正、松本義久、岩淵邦芳
  • Organizer: 第48回金沢医科大学医学会学術集会
  • Place of Presentation: 内灘
  • Year and Date: 2012-07-21
• [Presentation] Regulation of p21-mediated G1/S Checkpoint by 53BP1 (2012)
  • Author(s): Matsui T, Sunatani Y, Hashimoto M, Iwabuchi K
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] Mechanism of Apoptosis Induction via Regulation of ASAP Complex by XRCC4 (2012)
  • Author(s): Sunatani Y, Kamdar R P, Sharma M K, Matsui T, Hashimoto M, Matsumoto Y, Iwabuchi K
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] Silencing of STIM1 suppresses store operated calcium entry and cell growth of human epidermoid carcinoma A431 cells (2012)
  • Author(s): 吉田純子、岩淵邦芳
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] テロメア末端融合における53BP1とRad18の機能解析 (2012)
  • Author(s): 橋本光正、松井理、橋本優実、立石智、岩淵邦芳
  • Organizer: 日本放射線影響学会第55回大会
  • Place of Presentation: 仙台
• [Presentation] 53BP1によるp53機能の制御 (2012)
  • Author(s): 松井理、橋本優実、橋本光正、岩淵邦芳
  • Organizer: 日本放射線影響学会第55回大会
  • Place of Presentation: 仙台
• [Presentation] アポトーシスで生じたXRCC4N末断片によるDNA非損傷性アポトーシスの制御機構 (2012)
  • Author(s): 橋本優実、Kamdar R.P.、Sharma M. K.、松井理、橋本光正、松本義久、岩淵邦芳
  • Organizer: 日本放射線影響学会第55回大会
  • Place of Presentation: 仙台
• [Presentation] 低線量率放射線照射下におけるDNA2重鎖切断修復因子の役割 (2012)
  • Author(s): 冨田雅典、小林純也、岩淵邦芳、松本義久、足立典隆、高田穣、内海博司
  • Organizer: 日本放射線影響学会第55回大会
  • Place of Presentation: 仙台
• [Presentation] アイソトープ治療におけるリンパ球の放射線組織障害評価に関する検討 (2012)
  • Author(s): 道合万里子、渡邉直人、髙橋知子、谷口充、利波久雄、岩淵邦芳、萱野大樹、福岡誠、絹谷清剛
  • Organizer: 第71回日本医学放射線学会総会
  • Place of Presentation: 横浜
• [Presentation] アポトーシスで生じたXRCC4N末断片によるDNA非損傷性アポトーシスの制御機構 (2012)
  • Author(s): 橋本優実
  • Organizer: 日本放射線影響学会第55回大会
  • Place of Presentation: 東北大学川内北キャンパス（宮城県）
• [Presentation] 53BP1によるp53機能の制御 (2012)
  • Author(s): 松井理
  • Organizer: 日本放射線影響学会第55回大会
  • Place of Presentation: 東北大学川内北キャンパス（宮城県）
• [Presentation] テロメア末端融合における53BP1とRad18の機能解析 (2012)
  • Author(s): 橋本光正
  • Organizer: 日本放射線影響学会第55回大会
  • Place of Presentation: 東北大学川内北キャンパス（宮城県）
• [Presentation] 低線量率放射線照射下におけるDNA2重鎖切断修復因子の役割 (2012)
  • Author(s): 冨田雅典
  • Organizer: 日本放射線影響学会第55回大会
  • Place of Presentation: 東北大学川内北キャンパス（宮城県）
• [Presentation] Mechanism of apoptosis induction via regulation of ASAP complex by XRCC4 (2012)
  • Author(s): Yumi Sunatani
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡（福岡県）
• [Presentation] Regulation of p21-mediated G1/S checkpoint by 53BP1 (2012)
  • Author(s): Tadashi Matsui
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡（福岡県）
• [Presentation] Silencing of STIM1 suppresses store operated calcium entry and cell growth of human epidermoid carcinoma A431 cells (2012)
  • Author(s): 吉田純子
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌・さっぽろ芸文館・札幌市教育文化会館（北海道）
• [Presentation] アイソトープ治療におけるリンパ球の放射線組織障害評価に関する検討 (2012)
  • Author(s): 道合 万里子
  • Organizer: 第71回日本医学放射線学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] DNA二本鎖切断修復タンパク質XRCC4を介したアポトーシス制御機構の解明
  • Author(s): 橋本優実
  • Organizer: 金沢医科大学医学会第48回学術集会
  • Place of Presentation: 金沢医科大学（石川県）