Novel histone chaperone GRWD1 inhibits p53 and promotes tumorigenesis

• Project/Area Number: 15K18412
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kyushu University
• Principal Investigator: Sugimoto Nozomi 九州大学, 薬学研究院, 助教 (00633108)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: GRWD1 / p53 / 発がん / MDM2 / RPL11 / p53反応性プロモーター / がん / Purα

Outline of Final Research Achievements

GRWD1 is a novel histone chaperone that promotes MCM loading and may integrate regulations of cell cycle progression. We identified ribosomal protein RPL11 as a putative GRWD1 binding factor. Under nucleolar stress induced by treatment with low levels of actinomycin D or nutrient deprivation, RPL11 binds to and inhibits the MDM2 ubiquitin ligase, thereby promoting p53 stability. We found that GRWD1 inhibits RPL11-MDM2 interaction, abrogates RPL11-mediated p53 stabilization, and promotes tumorigenesis.

Research Products

• [Journal Article] GRWD1 negatively regulates p53 via the RPL11-MDM2 pathway and promotes tumorigenesis. (2017)
  • Author(s): Kayama K, Watanabe S, Takafuji T, Tsuji T, Hironaka K, Matsumoto M, Nakayama KI, Enari M, Kohno T, Shiraishi K, Kiyono T, Yoshida K, Sugimoto N, Fujita M.
  • Journal Title: EMBO Rep. Volume: 18 Issue: 1 Pages: 123-137
  • DOI: 10.15252/embr.201642444
  • Peer Reviewed
• [Journal Article] Nucleosome assembly and disassembly activity of GRWD1, a novel Cdt1-binding protein that promotes pre-replication complex formation. (2016)
  • Author(s): Aizawa M et al.
  • Journal Title: Biochim. Biophys. Acta Volume: 1863 Issue: 11 Pages: 2739-2748
  • DOI: 10.1016/j.bbamcr.2016.08.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cdt1-binding protein GRWD1 is a novel histone-binding protein that facilitates MCM loading through its influence on chromatin architecture. (2015)
  • Author(s): Sugimoto N, Maehara K, Yoshida K, Yasukouchi S, Osano S, Watanabe S, Aizawa M, Yugawa T, et al.
  • Journal Title: Nucleic Acids Res. Volume: 43 Issue: 12 Pages: 5898-5911
  • DOI: 10.1093/nar/gkv509
  • Peer Reviewed / Open Access
• [Presentation] GRWD1によるp53転写活性化能の抑制機構の解明 (2016)
  • Author(s): 廣中研介ら
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] GRWD1は核小体ストレス誘導因子RPL23タンパク質量を制御している (2016)
  • Author(s): 渡邉心也ら
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] ヒト細胞におけるpre-RC形成とfiringの時空間的制御のゲノムワイド解析 (2016)
  • Author(s): 杉本のぞみら
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] GRWD1 counteracts p53 via the RPL11-MDM2 pathway and promotes tumorigenesis (2016)
  • Author(s): Fujita M. et al.
  • Organizer: 10th 3R International Symposium
  • Place of Presentation: ホテル一畑（松江市）
  • Year and Date: 2016-11-13
  • Int'l Joint Research
• [Presentation] Genome-wide analysis for spatiotemporal regulation of the pre-RC formation and firing in human cells (2015)
  • Author(s): 杉本 のぞみ、他
  • Organizer: BMB2015
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2015-12-03
  • Invited
• [Presentation] ヒト細胞における複製前複合体(pre-RC)形成とfiringの時空間的制御のゲノムワイド解析 (2015)
  • Author(s): 杉本 のぞみ、他
  • Organizer: 第23回DNA複製・組換え・修復ワークショップ
  • Place of Presentation: 静岡県焼津市
  • Year and Date: 2015-10-20
• [Presentation] Genome-wide analysis for spatiotemporal regulation of the pre-RC formation and firing in human cells. (2015)
  • Author(s): Sugimoto, N. et al.
  • Organizer: Eukaryotic DNA replication & Genome maintenance on Cold Spring Harbor Laboratory Meeting
  • Place of Presentation: Cold Spring Harbor, USA
  • Year and Date: 2015-09-01
  • Int'l Joint Research
• [Presentation] Genome-scale analysis for spatiotemporal regulation of the pre-RC formation and firing in human cells. (2015)
  • Author(s): Sugimoto, N. et al.
  • Organizer: International Symposium on Non-Coding DNA and Chromosomal Integrity
  • Place of Presentation: 兵庫県淡路市
  • Year and Date: 2015-08-07
  • Int'l Joint Research
• [Remarks] ようこそ医薬細胞生化学研究室へ
  • URL: http://tansaku.phar.kyushu-u.ac.jp/saito/top.html
• [Remarks] ホームページ
  • URL: http://tansaku.phar.kyushu-u.ac.jp/saito/top.html