Role of p53-citrullination in human carcinogenesis

• Project/Area Number: 22300335
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor diagnosis
• Research Institution: The University of Tokyo
• Principal Investigator: MATSUDA Koichi 東京大学, 医科学研究所, 准教授 (90401257)
• Co-Investigator(Renkei-kenkyūsha): TANIKAWA Chizu 東京大学, 医科学研究所, 助教 (30422421)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2012: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: バイオマーカー / 53 / p53 / シトルリン化 / ヒストン / 自己抗体

Research Abstract

In this project, we have identified in vivo and in vitro citrullination of the arginine 3 residue of histone H4 (cit-H4R3) in response to DNA damage through the p53-PADI4 pathway. We also show DNA damage-induced citrullination of Lamin C. Padi4(-/-) mice exhibit resistance to radiation-induced apoptosis in the thymus. We also found frequent loss of function mutations in cancer tissues and cell lines. Our findings reveal the possible role of PADI4 as a tumor suppressor gene.

Research Products

• [Journal Article] Regulation of histone modification andchromatin structure by the p53-PADI4pathway. (2012)
  • Author(s): C. Tanikawa, M. Espinosa, A. Suzuki, K.Masuda, K. Yamamoto, E. Tsuchiya, K.Ueda, Y. Daigo, Y. Nakamura, K. Matsuda,
  • Journal Title: Nature communications Volume: 3 Pages: 676-676
• [Journal Article] CLCA2 as a p53-inducible senescencemediator. (2012)
  • Author(s): C. Tanikawa, H. Nakagawa, Y. Furukawa, Y. Nakamura, K. Matsuda
  • Journal Title: Neoplasia Volume: 14 Pages: 141-149
• [Journal Article] Regulation of histone modification and chromatin structure by the p53-PADI4 pathway (2012)
  • Author(s): Tanikawa C, Espinosa M, Suzuki A, Masuda K, Yamamoto K, Tsuchiya E, Ueda K, Daigo Y, Nakamura Y, Matsuda K.
  • Journal Title: Nat Commun. Volume: 3 Issue: 1 Pages: 676-676
  • DOI: 10.1038/ncomms1676
  • Peer Reviewed
• [Journal Article] CLCA2 as a p53-inducible senescence mediator (2012)
  • Author(s): C.Tanikawa, H.Nakagawa, Y.Furukawa, Y.Nakamura, K.Matsuda
  • Journal Title: Neoplasia Volume: 14 Issue: 2 Pages: 141-149
  • DOI: 10.1593/neo.111700
  • Peer Reviewed
• [Journal Article] Common variant in 6q26-q27 is associated with distal colon cancer in an Asian population. (2011)
  • Author(s): Cui R, Okada Y, Jang SG, Ku JL, Park JG, Kamatani Y, Hosono N, Tsunoda T, Kumar V, Tanikawa C, Kamatani N, Vamada R, Kubo M, Nakamura Y, Matsuda K.
  • Journal Title: GUT Volume: (In press)(掲載確定)
  • Peer Reviewed
• [Journal Article] Crosstalk of EDA-A2/XEDAR in the p53 signaling pathway (2010)
  • Author(s): C. Tanikawa, C. Ri, V. Kumar, Y. Nakamura, K. Matsuda
  • Journal Title: Molecular Cancer Research Volume: 8 Pages: 855-863
• [Journal Article] Crosstalk of EDA-A2/XEDAR in the p53 signaling pathway. (2010)
  • Author(s): Tanikawa C, Ri C, Kumar V, Nakamura Y, Matsuda K.
  • Journal Title: Mol Cancer Research Volume: 8 Pages: 855-863
  • Peer Reviewed
• [Journal Article] Genome-wide association study of hematological and biochemical traits in a Japanese population. (2010)
  • Author(s): Kamatani Y, Matsuda K, Okada Y, Kubo M, Hosono N, Daigo Y, Nakamura Y, Kamatani N.
  • Journal Title: Nature Genetics Volume: 42 Pages: 210-215
  • Peer Reviewed
• [Presentation] Regulation of histonemodification and chromatin structure byp53-PADI4 pathway (2012)
  • Author(s): Chizu Tanikawa, Yusuke Nakamura,Koichi Matsuda
  • Organizer: AACR
  • Place of Presentation: Chicago
  • Year and Date: 2012-04-04
• [Presentation] ゲノムワイド関連解析による癌感受性遺伝子の探索 (2012)
  • Author(s): 松田浩一
  • Organizer: 平成 23 年度 文科省がん支援活動・厚労省対がん10 カ年研究合同公開シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2012-01-31
• [Presentation] Regulation of histone modification and chromatin structure by the p53-PADI4 pathway (2012)
  • Author(s): Koichi Matsuda
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 札幌
  • Invited
• [Presentation] The role of histone citrrullination through p53/PADI4 network in carcinogenesis (2012)
  • Author(s): Chizu Tanikawa
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 札幌
  • Invited
• [Presentation] Regulation of histone modification and chromatin structure by the p53-PADI4 pathway (2012)
  • Author(s): Chizu Tanikawa
  • Organizer: AACR annual meeting
  • Place of Presentation: Chicago,USA
  • Invited
• [Presentation] p53-PADI4 pathway regulates histone modification and chromatin structure (2011)
  • Author(s): Chizu Tanikawa, Koichi Matsuda, Yataro Daigo, Yusuke Nakamura
  • Organizer: 日本癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] Functional analysis of the protein citrullination through p53-PADI4 pathway (2011)
  • Author(s): Chizu Tanikawa, Koichi Matsuda, Yusuke Nakanura
  • Organizer: American association for cancer research
  • Place of Presentation: Orland, USA
  • Year and Date: 2011-04-03
• [Presentation] Possible role of protein citrullination on autoantigenicity of tumor protein p53 (2010)
  • Author(s): Koichi Matsuda, Chizu Tanikawa, Cui Ri, Yusuke Nakamura
  • Organizer: 日本癌学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-22
• [Presentation] Regulation ofhistone modification and chromatinstructure by the p53-PADI4 pathway (2010)
  • Author(s): Koichi Matsuda, Chizu Tanikawa, YataroDaigo, Yusuke Nakamura
  • Organizer: 第71会日本癌学会
  • Place of Presentation: 札幌
  • Year and Date: 2010-09-21
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/nakamura/matsuda/index.html
• [Remarks] Matsuda Group / Nakamura Laboratory
  • URL: http://www.ims.u-tokyo.ac.jp/nakamura/matsuda/index.html
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/nakamura/matsuda/index.html