The molecular mechanisms of cellular aging and inhibition of cell growth mediated by transcription factor JDP2.

• Project/Area Number: 20570193
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: NAKADE Koji The Institute of Physical and Chemical Research, 遺伝子材料開発室, 協力研究員 (20392053)
• Co-Investigator(Kenkyū-buntansha): PAN Jhanzhi 独立行政法人理化学研究所, 遺伝子材料開発室, 専任研究員 (80373356)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 老化 / 細胞増殖 / 酸化ストレス / 転写 / エピジェネシス / セネッセンス / p16Ink4a / ストレス / クロマチン / シグナル伝達 / 細胞周期

Research Abstract

We have analyzed the molecular mechanisms of JDP2 in the regulation of cellular aging. We found that JDP2 induces the release of the histone methyltransferases, PRC1 and PRC2, from the p16Ink4a locus in response to oxidative stress, resulting the demethylation of histone H3 lysine 27 residue. This demethylation of histone causes the up-regulation of p16Ink4a and Arf, which are silenced by epigenetic effect in young cells. Finally, the cells are aged with senescent morphology.

Research Products

• [Journal Article] Suppression of cell-cycle progression by Jun dimerization protein-2 (JDP2) involves downregulation of cyclin-A2. (2010)
  • Author(s): Pan, J., K.Nakade, Y.C.Huang, Z.W.Zhu, S.Masuzaki, H.Hasegawa, T.Murata, A.Yoshiki, N.Yamaguchi, C.H.Lee, W.C.Yang, E.M.Tsai, Y.Obata, K.K.Yokoyama
  • Journal Title: Oncogene 29(47) Pages: 6245-56
  • Peer Reviewed
• [Journal Article] Epigenetic regulation of p16Ink4a and Arf by JDP2 in cellular senescence. (2010)
  • Author(s): K.Nakade, B.Wasylyk, K.K.Yokoyama
  • Journal Title: BioMolecular Concepts 1 Pages: 49-58
  • Peer Reviewed
• [Journal Article] Suppression of cell-cycle progression by Jun dimerization protein-2 (JDP2) involves downregulation of cyclin-A2. (2010)
  • Author(s): Pan, J., et al.
  • Journal Title: Oncogene. Volume: 29 Pages: 6245-6256
  • Peer Reviewed
• [Journal Article] Epigenetic regulation of p16Ink4a and Arf by JDP2 in cellular senescence. (2010)
  • Author(s): Nakade, K., et al.
  • Journal Title: BioMolecular Concepts Volume: 1 Pages: 49-58
  • Peer Reviewed
• [Journal Article] Role of histone chaperone JDP2 in replicative senescence (2010)
  • Author(s): K.Nakade, et al.
  • Journal Title: Current Topic of Biochemical Research (in press)
  • Peer Reviewed
• [Journal Article] JDP2 (Jun Dimerization Protein 2)-deficient mouse embryonic fibroblasts are resistant to replicative senescence. (2009)
  • Author(s): Nakade, K., J.Pan, T.Yamasaki, T.Murata, B.Wasylyk, K.K.Yokoyama
  • Journal Title: J Biol Chem 284(16) Pages: 10808-17
  • Peer Reviewed
• [Journal Article] The ubiquitously expressed bZIP inhibitor, JDP2, suppresses the transcription of its homologue immediate early gene counterpart, ATF3. (2009)
  • Author(s): Weidenfeld-Baranboim, K., T.Hasin, I.Darlyuk, R.Heinrich, O.Elhanani, J.Pan, K.K.Yokoyama, A.Aronheim
  • Journal Title: Nucleic Acids Res 37(7) Pages: 2194-203
  • Peer Reviewed
• [Journal Article] Phosphorylation of Activation Transcription Factor-2 at Serine 121 by Protein Kinase C Controls c-Jun-mediated Activation of Transcription. (2009)
  • Author(s): Yamasaki, T., A.Takahashi, J.Pan, N.Yamaguchi, K.K.Yokoyama
  • Journal Title: J Biol Chem 284(13) Pages: 8567-81
  • Peer Reviewed
• [Journal Article] Role of histone chaperone JDP2 in replicative senescence. (2009)
  • Author(s): Nakade, K., Pan, J, T.Yamasaki, M.Noguchi, S.Masuzaki, S.Kishikawa, T.Murata, Z.W.Zhu, X.Y.Chen, H.Hasegawa, N.Yamaguchi, E.M.Tsai, J.N.Lee, K.K.Yokoyama
  • Journal Title: Current Topics in Biochemical Research 11(1) Pages: 75-97
  • Peer Reviewed
• [Journal Article] JDP2(Jun dimerization protein 2)-deficient mouse embryonic fibroblasts are resistant to replicative senescence (2009)
  • Author(s): K.Nakade, K., et al.
  • Journal Title: Journal of Biological Chemistry 284 Pages: 10808-10817
  • Peer Reviewed
• [Journal Article] Jun dimerization protein 2-deficient mouse embryonic fibroblasts are resistant to replicative senescence
  • Author(s): K. Nakade, et al.
  • Journal Title: Journal of biological chemistry (印刷中)
  • Peer Reviewed
• [Journal Article] The ubiquitously expressed bZIP inhibitor, JDP2, suppresses the transcription of its homologue immediate early gene counterpart, ATF3
  • Author(s): K. Weidenfeld-Baranboim, et al.
  • Journal Title: Nucleic Acid Research (印刷中)
  • Peer Reviewed
• [Journal Article] Phosphorylation of activation transcription factor-2 at serine 121 by protein kinase C controls c-jun-mediated activation of transcription
  • Author(s): T. Yamasaki, et al.
  • Journal Title: Journal of biological chemistry (印刷中)
  • Peer Reviewed
• [Presentation] Jun dimerization protein 2 mediates replicative senescence (2010)
  • Author(s): 中出浩司、他
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド、神戸
  • Year and Date: 2010-12-08
• [Presentation] Jun dimerization protein 2 as a mediator of replicative senescence (2010)
  • Author(s): 中出浩司、他
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場、大阪
  • Year and Date: 2010-09-23
• [Presentation] Jun dimerization protein 2-deficient mouse embryonic fibroblasts are resistant to replicative senescence (2009)
  • Author(s): 中出浩司, et al.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜、横浜
  • Year and Date: 2009-12-09
• [Presentation] Jun dimerization protein 2-deficient mouse embryonic fibro blasts are resistant to replicative senescence (2009)
  • Author(s): 中出浩司, et al.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜、横浜
  • Year and Date: 2009-12-09
• [Presentation] 細胞老化を制御するAP1転写因子、Jun Dimerization Protein 2. (2008)
  • Author(s): 中出浩司, et al
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-10
• [Presentation] JDP2プロモーターによるトランスジェニックマウスでの小脳特異的なCre発現 (2008)
  • Author(s): 潘建治, et al
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-10
• [Presentation] 細胞老化を制御するAP1転写因子、Jun Dimerization Protein 2 (2008)
  • Author(s): 中出浩司, et al
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-10
• [Presentation] Generation and characterization of Nur77/TR3, JDP2 promoter-driven tissue-restricted Cre transgenic mice (2008)
  • Author(s): 潘建治, et al.
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-28
• [Presentation] The chromatin remodeling factor, Jun dimerization protein 2, regulates replicative senescence (2008)
  • Author(s): 中出浩司, et al.
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-28