ranscriptional regulation of HSF1 by polyADP-ribosylation enzyme PARP

• Project/Area Number: 25440010
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Yamaguchi University
• Principal Investigator: FUJIMOTO Mitsuaki 山口大学, 医学(系)研究科(研究院), 准教授 (80359900)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: HSF1 / PARP / 転写 / ポリADPリボシル化

Outline of Final Research Achievements

Heat shock response is regulated mainly at the level of transcription by heat shock factor 1 (HSF1). However, mechanisms of transcriptional induction of heat shock gene during heat shock (HSP) are not well known yet in mammalian.
I found that HSF1 forms a complex with PARP1, which has poly (ADP-ribose) polymerase activity, and PARP13, which lacks enzymatic activity. The depletion of PARP1 or PARP13 significantly reduced the induction of HSP70 mRNA during heat shock. Furthermore, HSF1 recruits PARP1 and PARP13 on HSP70 promoter region. In response to heat shock, PARP1 and PARP13 disappeared from the promoter and only PARP1 was redistributed on HSP70 gene body. HSF1-PARP complex associates with the change of chromatin components on HSP70 promoter in unstressed condition.

Research Products

• [Journal Article] Analysis of the Heat Shock Factor Complex in Mammalian HSP70 Promoter. (2015)
  • Author(s): Fujimoto M, Takii R, Hayashida N, Nakai A.
  • Journal Title: Methods Mol Biol. Volume: 1292 Pages: 53-65
  • DOI: 10.1007/978-1-4939-2522-3_4
  • ISBN: 9781493925216, 9781493925223
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mitochondrial SSBP1 protects cells from proteotoxic stresses by potentiating stress-induced HSF1 transcriptional activity. (2015)
  • Author(s): Tan, K., Fujimoto, M., Takii, R., Takaki, E., Hayashida, N., Nakai, A.
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 6580-6594
  • DOI: 10.1038/ncomms7580
  • NAID: 120005822836
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ATF1 modulates the heat shock response by regulating the stress-inducible HSF1-transcription complex (2015)
  • Author(s): R. Takii, M. Fujimoto, K. Tan, E. Takaki, N. Hayashida, R. Nakato, K. Shirahige, and A. Nakai
  • Journal Title: Mol. Cell. Biol. Volume: 35 Issue: 1 Pages: 11-25
  • DOI: 10.1128/mcb.00754-14
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Heat shock factor 1 is required for migration and invasion of human melanoma in vitro and in vivo (2014)
  • Author(s): Y. Nakamura, M. Fujimoto, S. Fukushima, A. Nakamura, N. Hayashida, R. Takii, E. Takaki, A. Nakai, M. Muto
  • Journal Title: Cancer Lett. Volume: 354 Issue: 2 Pages: 329-335
  • DOI: 10.1016/j.canlet.2014.08.029
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Heat shock factor 1 accelerates hepatocellular carcinoma development by activating nuclear factor κB/mitogen-activated protein kinase. (2014)
  • Author(s): Chuma M, Sakamoto N, Nakai A, Hige S, Nakanishi M, Natsuizaka M, Suda G, Sho T, Hatakaka K, Matsuno Y, Yokoo H, Kamiyama T, Taketomi A, Fujii G, Tashiro K, Hikiba Y, Fujimoto M, Asaka M, Maeda S
  • Journal Title: Carcinogenesis Volume: Epub ahead of print Issue: 2 Pages: 272-281
  • DOI: 10.1093/carcin/bgt343
  • Peer Reviewed
• [Journal Article] Chicken IL-6 is a heat-shock gene (2013)
  • Author(s): Prakasam R, Fujimoto M. Takii R, Hayashida N, Takaki E, Tan K, Wu F, Inouye S, Nakai A.
  • Journal Title: FEBS Lett Volume: 587(21) Issue: 21 Pages: 3541-3547
  • DOI: 10.1016/j.febslet.2013.09.012
  • Peer Reviewed
• [Presentation] タンパク質毒性ストレス応答とDNA損傷ストレス応答の接点 (2015)
  • Author(s): 藤本 充章
  • Organizer: 第88回日本生化学会大会 ・ 第38回日本分子生物学会 合同大会
  • Place of Presentation: 神戸ポートピアホテル、神戸国際会議場、神戸国際展示場、神戸商工会議場 (兵庫県・神戸市）
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] HSF1-PARP相互作用がHSP70遺伝子座のクロマチン構成を調節する (2014)
  • Author(s): 藤本 充章
  • Organizer: 日本生化学会大会
  • Place of Presentation: 国立京都国際会館（ 京都府）
  • Year and Date: 2014-10-16 – 2014-10-17
• [Presentation] HSF1-PARP13複合体は非ストレス下で熱ショック誘導に必要なPARP1を留めている (2013)
  • Author(s): 藤本 充章
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド ・ 神戸
• [Presentation] PARP13はHSF1を介するHSP70誘導に必要である (2013)
  • Author(s): 藤本 充章
  • Organizer: 日本生化学会大会
  • Place of Presentation: パシフィコ横浜 ・ 横浜
• [Remarks] 山口大学大学院医学系研究科医化学分野研究室ホームページ
  • URL: http://ds22.cc.yamaguchi-u.ac.jp/~seika2/index-3.html
• [Remarks] 山口大学大学院医学系研究科医化学分野
  • URL: http://ds22.cc.yamaguchi-u.ac.jp/~seika2/index-3.html
• [Remarks] 山口大学大学院医学系研究科医化学分野
  • URL: http://ds22.cc.yamaguchi-u.ac.jp/~seika2/index-3.html