Functional role of lipid second messenger metabolizing enzyme in cell cycle and stress response

2011 Fiscal Year Final Research Report

• Project/Area Number: 20390050
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Yamagata University
• Principal Investigator: GOTO Kaoru 山形大学, 医学部, 教授 (30234975)
• Co-Investigator(Kenkyū-buntansha): ISEKI Ken 山形大学, 医学部, 准教授 (70332921) ; HOZUMI Yasukazu 山形大学, 医学部, 准教授 (00372334) ; OKADA Masashi 山形大学, 医学部, 講師 (70512614) ; TANAKA Toshiaki 山形大学, 医学部, 助教 (70536987)
• Project Period (FY): 2008 – 2011
• Keywords: 細胞周期 / ストレス応答 / 脂質代謝酵素

Research Abstract

Diacylglycerol kinase (DGK), an enzyme that phosphorylates diacylglycerol to phosphatidic acid, is involved in many pathophysiological cellular responses, such as cancer and apoptosis. Our previous studies show that DGKζ, which contains a nuclear localization signal, is localized in the nucleus of hippocampal neurons but rapidly translocates from the nucleus to the cytoplasm and disappears in the early phase of ischemia, suggesting its implication in an apoptotic process. In this study we investigated the functional link between DGKζ cytoplasmic translocation and p53 that acts as the hub of various stress pathways. We found that cytoplasmic DGKζ induces cytoplasmic localization of p53 after DNA damage and suppresses p53 induction. In neurons, down-regulation of nuclear DGK. after excitotoxic stress leads to aberrant cell cycle reentry, which results in cell death. These findings suggest that DGKζ cytoplasmic translocation exerts distinct effects on signal transduction both in the cytoplasm and the nucleus.

Research Products

• [Journal Article] Altered expression of diacylglycerol kinase isozymes in regenerating liver (2012)
  • Author(s): Nakano T, Hozumi Y, Iwazaki K, Okumoto K, Iseki K, Saito T, Kawata S, Wakabayashi I, Goto K.
  • Journal Title: J Histochem Cytochem Volume: 60 Pages: 130-8
  • DOI: doi:10.1369/0022155411429154.
  • Peer Reviewed
• [Journal Article] NMDA receptor-mediated Ca(2+) influx triggers nucleocytoplasmic translocation of diacylglycerol kinase ζ under oxygen-glucose deprivation conditions, an in vitro model of ischemia, in rat hippocampal slices (2012)
  • Author(s): Suzuki Y, Yamazaki Y, Hozumi Y, Okada M, Tanaka T, Iseki K, Ohta N, Aoyagi M, Fujii S, Goto K.
  • Journal Title: Histochem CellBiol Volume: 137 Pages: 499-511
  • DOI: doi:10.1007/s00418-011-0907-y.
  • Peer Reviewed
• [Journal Article] DGKζ is involved in LPS-activated phagocytosis through IQGAP1/Rac1 pathway (2012)
  • Author(s): Okada M, Hozumi Y, Iwazaki K, Misaki K, Yanagida M, Araki Y, Watanabe T, Yagisawa H, Topham MK, Kaibuchi K, Goto K.
  • Journal Title: Biochem Biophys Res Commun Volume: 420 Pages: 479-84
  • DOI: doi:10.1016/j.bbrc.2012.03.057.
  • Peer Reviewed
• [Journal Article] Diacylglycerol kinase β in neurons: functional implications at the synapse and in disease (2012)
  • Author(s): Hozumi Y, Goto K.
  • Journal Title: Adv Biol Regul Volume: 52 Pages: 315-25
  • DOI: doi:10.1016/j.jbior.2012.03.003.
  • Peer Reviewed
• [Journal Article] DGKζ is degraded through the cytoplasmic ubiquitin-proteasome system under excitotoxic conditions, which causes neuronal apoptosis because of aberrant cell cycle reentry (2012)
  • Author(s): Okada M, Hozumi Y, Tanaka T, Suzuki Y, Yanagida M, Araki Y, Evangelisti C, Yagisawa H, Topham MK, Martelli AM, Goto K.
  • Journal Title: Cell Signal Volume: 24 Pages: 1573-82
  • DOI: doi:10.1016/j.cellsig.2012.03.021.
  • Peer Reviewed
• [Journal Article] Involvement of diacylglycerol kinase γ in modulation of iNOS synthesis in Golgi apparatus of vascular endothelial cells (2012)
  • Author(s): Nakano T, Hozumi Y, Goto K, Wakabayashi I
  • Journal Title: Naunyn Schmiedebergs Arch Pharmacol Volume: 385 Pages: 787-95
  • DOI: doi:10.1007/s00210-012-0760-0.
  • Peer Reviewed
• [Journal Article] The emerging multiple roles of nuclear Akt (2012)
  • Author(s): Martelli AM, Tabellini G, Bressanin D, Ognibene A, Goto K, Cocco L, Evangelisti C.
  • Journal Title: Biochim Biophys Acta Volume: 1823 Pages: 2168-78
  • DOI: doi:10.1016/j.bbamcr.2012.08.017.
  • Peer Reviewed
• [Journal Article] Inhibition of thrombin-induced Ca^^<2+> influx in platelets by R59949, an inhibitor of diacylglycerol kinase (2012)
  • Author(s): Marumo M, Nakano T, Takeda Y, Goto K, Wakabayashi I.
  • Journal Title: J Pharm Pharmacol Volume: 64 Pages: 855-861
  • DOI: doi:10.1111/j.2042-7158.2012.01485.x.
  • Peer Reviewed
• [Journal Article] Excitotoxicity by kainate-induced seizure causes diacylglycerol kinase ζ to shuttle from the nucleus to the cytoplasm in hippocampal neurons (2011)
  • Author(s): Saino-Saito S, Hozumi Y, Goto K.
  • Journal Title: Neurosci Lett Volume: 494 Pages: 185-9
  • DOI: doi:10.1016/j.neulet.2011.02.062.
  • Peer Reviewed
• [Journal Article] Nuclear relocation of DGKζ in cardiomyocytes under conditions of ischemia/reperfusion (2011)
  • Author(s): Akiyama H, Hozumi Y, Nakano T, Kubota I, Goto K.
  • Journal Title: Histol Histophathol Volume: 26 Pages: 1383-1390
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/21938675
  • Peer Reviewed
• [Journal Article] Nuclear phosphoinositides and their roles in cell biology and disease (2011)
  • Author(s): Martelli AM, Ognibene A, Buontempo F, Fini M, Bressanin D, Goto K, McCubrey JA, Cocco L, Evangelisti C.
  • Journal Title: Critical Reviews in Biochemistry and Molecular Biology Volume: 46 Pages: 436-57
  • DOI: doi:10.3109/10409238.2011.609530.
  • Peer Reviewed
• [Journal Article] NAP Interaction of nucleosome assembly proteins abolishes nuclear localization of DGKζ by attenuating its association with importins (2011)
  • Author(s): Okada M, Hozumi Y, Ichimura T, Tanaka T, Hasegawa H, Yamamoto M, Takahashi N, Iseki K, Yagisawa H, Shinkawa T, Isobe T, Goto K.
  • Journal Title: Exp Cell Res Volume: 317 Pages: 2853-63
  • DOI: doi:10.1016/j.yexcr.2011.09.014.
  • Peer Reviewed
• [Journal Article] Signaling Cascade of Diacylglycerol Kinase beta in the Pituitary Intermediate Lobe: Dopamine D2 Receptor/ Phospholipase C-beta4/ Diacylglycerol Kinase-beta/ Protein Kinase C-alpha (2010)
  • Author(s): Hozumi Y, Watanabe M, Goto K.
  • Journal Title: J HistochemCytochem Volume: 58 Pages: 119-129
  • DOI: doi:10.1369/jhc.2009.954347.
  • Peer Reviewed
• [Journal Article] Identification of a functional nuclear export sequence in diacylglycerol kinase-zeta (2010)
  • Author(s): Evangelisti C, Gaboardi GC, Billi AM, Ognibene A, Goto K, Tazzari PL, McCubrey JA, Martelli AM.
  • Journal Title: Cell Cycle Volume: 9 Pages: 1-6
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/20023381
  • Peer Reviewed
• [Journal Article] TIS21/BTG2/PC3 and cyclin D1 are key determinants of nuclear diacylglycerol kinase-zeta-dependent cell cycle arrest (2009)
  • Author(s): Evangelisti C, Astolfi A, Gaboardi GC, Tazzari P, Pession A, Goto K, Martelli AM.
  • Journal Title: Cellular Signaling Volume: 21 Pages: 801-9
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/19263516
  • Peer Reviewed
• [Journal Article] Brain trauma induces expression of diacylglycerol kinase zeta in microglia (2009)
  • Author(s): Nakano T, Iseki K, Hozumi Y, Kawamae K, Wakabayashi I, Goto K.
  • Journal Title: Neurosci Lett Volume: 461 Pages: 110-5
  • DOI: doi:10.1016/j.neulet.2009.06.001.
  • Peer Reviewed
• [Journal Article] Diacylglycerol kinase beta promotes dendritic outgrowth and spine maturation in developing hippocampal neurons (2009)
  • Author(s): Hozumi Y, Watanabe M, Otani K, Goto K.
  • Journal Title: BMCNeurosci Volume: 10 Pages: 99
  • DOI: doi:10.1186/1471-2202-10-99.
  • Peer Reviewed
• [Presentation] Cytoplasmic localization of diacylglycerol kinase zeta suppresses p53 induction after DNA damage (2012)
  • Author(s): Tanaka T, Goto K
  • Organizer: 42th Annual Meeting of Neuroscience, Convention Center
  • Place of Presentation: New Orleans, USA
  • Year and Date: 20121013-17
• [Presentation] Subcellular localization of Diacylglycerol kinase ε in transfected neurons (2012)
  • Author(s): Matsui H, Hozumi Y, Iseki K, Goto K
  • Organizer: 42th Annual Meeting of Neuroscience, Convention Center
  • Place of Presentation: New Orleans, USA
  • Year and Date: 20121013-17
• [Presentation] Expression and localization of diacylglycerol kinase in rat retina (2012)
  • Author(s): Hozumi Y, Goto K
  • Organizer: 42th Annual Meeting of Neuroscience, Convention Center
  • Place of Presentation: New Orleans, USA
  • Year and Date: 20121013-17
• [Presentation] Functional significance of diacylglycerol kinase in stress response (2011)
  • Author(s): Goto K
  • Organizer: The 116th Annual Meeting of The Japanese Association of Anatomists and the 88th Annual Meeting of The Physiological Society of Japan
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 20110328-30
• [Presentation] Cytoplasmic diacylglycerol kinase ζ suppresses p53 stability and apoptosis (2011)
  • Author(s): Tanaka T, Goto K
  • Organizer: Gordon Conference, Ventura
  • Place of Presentation: CA, USA
  • Year and Date: 20110227-0304
• [Presentation] Nuclear assemblyproteinはDGKζの細胞内局在を制御する (2010)
  • Author(s): 岡田雅司、後藤薫
  • Organizer: 第115回日本解剖学会総会
  • Place of Presentation: 岩手医科大学、盛岡
  • Year and Date: 20100328-30
• [Presentation] DGKζ結合蛋白 NAP1とNAP2の脳内局在解析 (2010)
  • Author(s): 高橋信也、後藤薫
  • Organizer: 第115回日本解剖学会総会
  • Place of Presentation: 岩手医科大学、盛岡
  • Year and Date: 20100328-30
• [Presentation] Nucleocytoplasmic translocation of diacylglycerol kinase zeta under oxygen and glucose deprivation in rat hippocampal slices (2009)
  • Author(s): Yusuke Suzuki, Yoshihiko Yamazaki, Kenya Kaneko, Satoshi Fujii, Ken Iseki, Kaoru Goto
  • Organizer: 39th Annual Meeting of Neuroscience, Convention Center
  • Place of Presentation: Chicago, USA
  • Year and Date: 20091017-21
• [Presentation] Cytoplasmic lipid kinase suppresses p53 stability (2009)
  • Author(s): Toshiaki Tanaka, Masashi Okada, Kaoru Goto
  • Organizer: 39th Annual Meeting of Neuroscience, Convention Center
  • Place of Presentation: Chicago, USA
  • Year and Date: 20091017-21
• [Presentation] Diacylglycerol kinase beta promotes dendritic outgrowth and spine maturation in developing hippocampal neurons (2009)
  • Author(s): Yasukazu Hozumi, Kaoru Goto
  • Organizer: 39th Annual Meeting of Neuroscience, Convention Center
  • Place of Presentation: Chicago, USA
  • Year and Date: 20091017-21