Regulation of adaptive responses to hypoxia and glucose deprivation by NAD-dependent deacetylase SIRT7

• Project/Area Number: 24590074
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Hokkaido University
• Principal Investigator: NAKAGAWA KOJI 北海道大学, 薬学研究科(研究院), 講師 (80360949)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Masanobu 北海道医療大学, 看護福祉学部, 教授 (80241321)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 低酸素応答 / 低グルコース応答 / SIRT7 / 脱アセチル化酵素 / HIF-1 / MDM2 / CHMP5 / ＨＩＦ－１ / ＳＩＲＴ７ / 癌遺伝子 / 癌抑制遺伝子

Outline of Final Research Achievements

In this project, we investigated the physical and functional interactions between SIRT7 (sirtuin-7) deacetylase and HIF-1(hypoxia inducible factor-1). It was found that SIRT7 physically associates with HIF-1α and enhances the expression of HIF-1-target genes. Moreover, we also found that SIRT7 directly associates with E3-ubiquitin ligase MDM2 (murine double minute 2), which is known to enhance the transcriptional activity of HIF-1, and increases the protein stability of MDM2.

Research Products

• [Journal Article] 医学用語解説 脱アセチル化酵素SIRT7 (2014)
  • Author(s): 中川宏治、武田宏司
  • Journal Title: G.I.Research Volume: ２２ Pages: 69-71
• [Journal Article] Hypoxia-inducible Factors Activate CD133 Promoter through ETS Family Transcription Factors (2013)
  • Author(s): Ohnishi S, Maehara O, Nakagawa K, Kameya A, Otaki K, Fujita H, Higashi R, Takagi K, Asaka M, Sakamoto N, Kobayashi M, Takeda H
  • Journal Title: Plos One Volume: 8 Issue: 6 Pages: e66255-e66255
  • DOI: 10.1371/journal.pone.0066255
  • NAID: 120005326763
  • Peer Reviewed
• [Journal Article] Enhancement of in vitro cell motility and invasiveness of human malignant pleural mesothelioma cells through the HIF-1α-MUC1 pathway. (2013)
  • Author(s): Goudarzi H, Iizasa H, Furuhashi M, Nakazawa S, Nakane R, Liang S, Hida Y, Yanagihara K, Kubo T, Nakagawa K, Kobayashi M, Irimura T, Hamada J.
  • Journal Title: Cancer Lett Volume: 339 Issue: 1 Pages: 82-91
  • DOI: 10.1016/j.canlet.2013.07.020
  • Peer Reviewed
• [Journal Article] The nuclear protein Artemis promotes AMPK activation by stabilizing the LKB1-AMPK complex (2012)
  • Author(s): Nakagawa K, Uehata Y, Natsuizaka M, Kohara T, Darmanin S, Asaka M, Takeda H, Kobayashi M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 427 Issue: 4 Pages: 790-795
  • DOI: 10.1016/j.bbrc.2012.09.140
  • Peer Reviewed
• [Journal Article] Polyubiquitination of the B-Cell Translocation Gene 1 and 2 Proteins Is Promoted by the SCF Ubiquitin Ligase Complex Containing βTrCP (2012)
  • Author(s): Sasajima H, Nakagawa K, Kashiwayanagi M, Yokosawa H.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 35 Issue: 9 Pages: 1539-1545
  • DOI: 10.1248/bpb.b12-00330
  • NAID: 130001872080
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed
• [Journal Article] Impaired ghrelin signaling is associated with gastrointestinal dysmotility in rats with gastroesophageal reflux disease. (2012)
  • Author(s): Nahata M, Muto S, Oridate N, Ohnishi S, Nakagawa K, Sadakane C, Saegusa Y, Hattori T, Asaka M, Takeda H.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol. Volume: 303 Issue: 1 Pages: G42-G53
  • DOI: 10.1152/ajpgi.00462.2011
  • Peer Reviewed
• [Journal Article] Rikkunshito as a ghrelin enhancer. (2012)
  • Author(s): Takeda H, Muto S, Nakagawa K, Ohnishi S, Sadakane C, Saegusa Y, Nahata M, Hattori T, Asaka M.
  • Journal Title: Methods Enzymol. Volume: 514 Pages: 333-351
  • DOI: 10.1016/b978-0-12-381272-8.00021-0
  • Peer Reviewed