Functional Significance of Interaction between MYCN and AZ2 in Neuroblastoma Cells

• Project/Area Number: 15K09666
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Jikei University School of Medicine
• Principal Investigator: MURAI NORIYUKI 東京慈恵会医科大学, 医学部, 講師 (60300927)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 神経芽細胞腫 / MYCN / アンチザイム / ポリアミン / ユビキチン非依存的タンパク質分解 / アンチザイム２ / プロテアソーム / ユビキチン依存的分解 / がんの増殖 / がんの悪性度 / ユビキチン非依存的分解

Outline of Final Research Achievements

It has been known that high expression of MYCN in neuroblastoma patient correlates with poor prognosis. We have previously found that AZ2 interacts with c-Myc and accelerates its degradation in ubiquitin-independent manner. It has been reported that high expression of AZ2 mRNA in neuroblastoma patients correlates with good prognosis. Then we hypothesized that AZ2 can also interact with MYCN and accelerates MYCN degradation in neuroblastoma. Through this study, we identified as follows. 1) AZ2 interacts with MYCN in the nuclear and nucleolar in neuroblastoma cells. 2) AZ2 can accelerates MYCN degradation by the proteasome in a ubiquitin-independent manner. 3) Knocking down of AZ2 in neuroblastoma cell line with siRNA stabilized the level of MYCN and increased the colony number and size more than two-fold compared to that of control cells in soft-agar colony formation assay.
Thus AZ2 have the potential to regulate neuroblastoma cell growth through accelerating the degradation of MYCN.

Research Products

• [Journal Article] Novel ubiquitin-independent nucleolar c-Myc degradation pathway mediated by antizyme 2 (2018)
  • Author(s): Murai Noriyuki、Murakami Yasuko、Tajima Ayasa、Matsufuji Senya
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 3005-3005
  • DOI: 10.1038/s41598-018-21189-0
  • Peer Reviewed / Open Access
• [Journal Article] Polyamine regulating protein antizyme binds to ATP citrate lyase to accelerate acetyl-CoA production in cancer cells (2016)
  • Author(s): Tajima, A., Murai, N., Murakami, Y., Iwamoto, T., Migita, T.,Matsufuji, S.
  • Journal Title: Biochem Biophys Res Commun Volume: 471 Issue: 4 Pages: 646-51
  • DOI: 10.1016/j.bbrc.2016.02.084
  • Peer Reviewed / Open Access
• [Presentation] 神経芽細胞腫増殖におけるMYCNとアンチザイム2の関与 (2018)
  • Author(s): 村井法之
  • Organizer: 日本ポリアミン学会 第９回年会
  • Invited
• [Presentation] Antizyme-Interacting Proteins in Cancer Cells (2017)
  • Author(s): Noriyuki Murai
  • Organizer: Gordon Research Conference
  • Int'l Joint Research / Invited
• [Presentation] Novel ubiquitin-independent nucleolar c-Myc degradation pathway (2016)
  • Author(s): Murai N
  • Organizer: 4th International Conference on Polyamines: Biochemical, Physiological and Clinical Perspectives
  • Place of Presentation: Tivoli(Rome)
  • Year and Date: 2016-09-05
  • Int'l Joint Research
• [Presentation] アンチザイム２とc-MYCの核小体共局在とユビキチン非依存的分解 (2015)
  • Author(s): 村井法之
  • Organizer: 第38回日本分子生物学会年会第88回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] Interaction between c-MYC and Antizyme 2 in the nucleolus. (2015)
  • Author(s): Murai N.
  • Organizer: Gordon Research Conference -Polyamine-
  • Place of Presentation: Waterville Valley NH ＵＳＡ
  • Year and Date: 2015-06-17
  • Int'l Joint Research