Physiological function of PAD4, a rheumatoid arthritis-related protein, and its molecular mechanisms.

• Project/Area Number: 21790943
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: The University of Tokyo
• Principal Investigator: NAKASHIMA Katsuhiko The University of Tokyo, 大学院・医学系研究科, 助教 (90528035)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: リウマチ学 / エピジェネティクス / シトルリン化 / PAD4 / 血球分化 / PADI4 / リウマチ / 造血幹細胞 / ペプチジルアルギニンデイミナーゼ

Research Abstract

PAD4 was predominantly expressed in HSC while less in the progenitor cells. Moreover, frequency of HSC in PAD4-deficient mice is higher than that in wild-type mice. Furthermore, the expression levels of some genes related to the cell proliferation were changed in PAD4-deficient HSC compared to wild-type HSC. These results suggested that PAD4 might maintain HSC proliferation in bone marrow by regulation of the gene expression mediated by histone citrullination.

Research Products

• [Journal Article] Small RNA-mediated regulation of iPS cell generation. (2011)
  • Author(s): Zhonghan Li, Chao-shun Yang, Katsuhiko Nakashima, Tariq M Rana.
  • Journal Title: EMBO J. 30 Pages: 823-834
  • Peer Reviewed
• [Journal Article] Small RNA-mediated regulation of iPS cell generation. (2011)
  • Author(s): Zhonghan Li, Chao-shun Yang, Katsuhiko Nakashima, Tariq M Rana
  • Journal Title: EMBO J. Volume: 30 Pages: 823-834
  • Peer Reviewed
• [Journal Article] Macrophage-derived AIM is endocytosed into adipocytes and decreases lipid droplets via inhibition of fatty acid synthase activity. (2010)
  • Author(s): Jun Kurokawa, Satoko Arai, Katsuhiko Nakashima, Hiromichi Nagano, Akemi Nishijima, Keishi Miyata, Rui Ose, Mayumi Mori, Naoto Kubota, Takashi Kadowaki, Yuichi Oike, Hisashi Koga, Maria Febbraio, Toshihiko Iwanaga, Toru Miyazaki.
  • Journal Title: Cell Metabolism 11 Pages: 479-492
  • Peer Reviewed
• [Journal Article] The death effector domain-containing DEDD forms a complex with Akt and Hsp90, and supports their stability. (2010)
  • Author(s): Nobuya Kurabe, Mayumi Mori, Jun Kurokawa, Kaori Taniguchi, Hisatoshi Aoyama, Kazuhiro Atsuda, Akemi Nishijima, Nariaki Odawara, Saori Harada, Katsuhiko Nakashima, Satoko Arai, Toru Miyazaki.
  • Journal Title: Biochem.Biophys.Res.Commun. 391 Pages: 1708-1713
  • Peer Reviewed
• [Journal Article] Macrophage-derived AIM is endocytosed into adipocytes and decreases lipid droplets via inhibition of fatty acid synthase activity. (2010)
  • Author(s): Jun Kurokawa, Satoko Arai, Katsuhiko Nakashima, Hiromichi Nagano, Akemi Nishijima, Keishi Miyata, Rui Ose, Mayumi Mori, Naoto Kubota, Takashi Kadowaki, Yuichi Oike, Hisashi Koga, Maria Febbraio, Toshihiko Iwanaga, Toru Miyazaki
  • Journal Title: Cell Metabolism Volume: 11 Pages: 479-492
  • Peer Reviewed
• [Journal Article] The death effector domain-containing DEDD forms a complex with Akt and Hsp90, and supports their stability. (2010)
  • Author(s): Nobuya Kurabe, Mayumi Mori, Jun Kurokawa, Kaori Taniguchi, Hisatoshi Aoyama, Kazuhiro Atsuda, Akemi Nishijima, Nariaki Odawara, Saori Harada, Katsuhiko Nakashima, Satoko Arai, Toru Miyazaki
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 391 Pages: 1708-1713
  • Peer Reviewed
• [Journal Article] Dynamic expression of peptidylarginine deiminase 2 in human monocytic leukemia THP-1 cells during macrophage differentiation. (2009)
  • Author(s): Ikuko Hojo-Nakashima, Ryo Sato, Katsuhiko Nakashima (corresponding author), Teruki Hagiwara, Michiyuki Yamada.
  • Journal Title: J.Biochem. 146 Pages: 471-479
  • Peer Reviewed
• [Presentation] AIMの翻訳後分子修飾の脂肪細胞における生理活性に対する意義 (2010)
  • Author(s): 長野広通, 黒川淳, 中島克彦, 新井郷子, 宮崎徹
  • Organizer: 第33回に本分子生物学会年会・第83回日本生化学会年会合同大会
  • Place of Presentation: 神戸ポートアイランド(兵庫)
  • Year and Date: 2010-12-10
• [Presentation] The role of PAD4 in hematopoietic stem cells and its molecular mechanisms. (2010)
  • Author(s): Katsuhiko Nakashima, Akari Suzuki, Takeshi Urano, Osamu Ohara, Kazuhiko Yamamoto, Toru Miyazaki.
  • Organizer: 第33回に本分子生物学会年会・第83回日本生化学会年会合同大会
  • Place of Presentation: 神戸ポートアイランド(兵庫)
  • Year and Date: 2010-12-09
• [Presentation] The role of PAD4 in hematopoietic stem cells and its molecular mechanisms. (2010)
  • Author(s): Katsuhiko Nakashima, Akari Suzuki, Takeshi Urano, Osamu Ohara, Kazuhiko Yamamoto, Toru Miyazaki.
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2010-12-09
• [Presentation] A new role of AIM, an apoptosis inhibitor expressed by macrophage, on adipocytes. (2009)
  • Author(s): 黒川淳, 新井郷子, 中島克彦, 宮崎徹
  • Organizer: 第32回に本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2009-12-11
• [Presentation] To identify the pathogenic T lymphocytes for metabolic syndrome. (2009)
  • Author(s): 谷口香織, 中島克彦, 新井郷子, 宮崎徹
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2009-12-11
• [Presentation] リウマチ関連タンパク質PAD4の血球分化、機能への関与 (2009)
  • Author(s): 中島克彦, 鈴木亜香里, 山本一彦, 宮崎徹
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド(兵庫)
  • Year and Date: 2009-10-23
• [Presentation] 肥満におけるアポトーシス抑制因子AIM/CD5Lの役割 (2009)
  • Author(s): 黒川淳, 新井郷子, 中島克彦, 門脇孝, 岩永敏彦, 宮崎徹
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド(兵庫)
  • Year and Date: 2009-10-23
• [Presentation] リウマチ関連タンパク質PAD4の血球分化、機能への関与 (2009)
  • Author(s): 中島克彦
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2009-10-23