Molecular mechanism of tumorigenesis related to aberrant nuclear-cytoplasmic transport

• Project/Area Number: 24790309
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: University of Tsukuba
• Principal Investigator: SAITO Shoko 筑波大学, 医学医療系, 助教 (70344885)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 核―細胞質間物質輸送 / 細胞がん化 / 核膜孔複合体 / 核外輸送 / CRM1/XPO1 / NF-kB / 核―細胞質間輸送 / 白血病 / XPO1/CRM1 / NXF1/TAP / リボソーム / NESタンパク質 / 核－細胞質間輸送 / エクスポーチン / mRNA

Outline of Final Research Achievements

To elucidate the relationship between aberrant nuclear-cytoplasmic transport and oncogenesis, we examined cellular functions of fusion proteins, SET-NUP214 and DEK-NUP214. NUP214 is one of the nuclear pore complex components, and critical for efficient nuclear-cytoplasmic export of macromolecules.
We found SET-NUP214 and DEK-NUP214 interact with not only XPO1/CRM1 but also NXF1/TAP preferentially among several nuclear transport receptors. We observed that nuclear accumulation of endogenous proteins harboring NES in cells expressing SET-NUP214 or DEK-NUP214. By contrast, nuclear accumulation of mRNA was not so clear in cells expressing SET-NUP214 or DEK-NUP214. We also observed that endogenous NF-κB complex, whose subcellular localization is regulated in a XPO1-dependent manner, accumulates in nuclei in cells expressing SET-,DEK-NUP214. NF-κB activity was partially suppressed in the presence of SET-,DEK-NUP214.

Research Products

• [Journal Article] Phase locking and multiple oscillating attractors for the coupled mammalian clock and cell cycle. (2014)
  • Author(s): Feillet C, Krusche P, Tamanini F, Janssens RC, Downey MJ, Martin P, Teboul M, Saito S, Lévi FA, Bretschneider T, van der Horst GT, Delaunay F, Rand DA.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 111 Issue: 27 Pages: 9828-33
  • DOI: 10.1073/pnas.1320474111
  • Peer Reviewed
• [Journal Article] Synchronisation and control of proliferation in cycling cell population models with age structure (2012)
  • Author(s): Billy F, Clairambault J, Fercoq O, Gaubert S, Lepoutre T, Ouillon T, Saito S
  • Journal Title: Math. Comp. Simul. Volume: Available online Pages: 0-0
  • DOI: 10.1016/j.matcom.2012.03.005
  • Peer Reviewed
• [Presentation] Aberrant nuclear-cytoplasmic transport by nup214-fusion gene products found in leukemia (2014)
  • Author(s): Shoko Saito, Cigdem Sadik, Kyosuke Nagata
  • Organizer: Cold Spring Harbor Laboratory meeting, Nuclear Organization & Function
  • Place of Presentation: Cold Spring Harbor, USA
  • Year and Date: 2014-08-19 – 2014-08-23
• [Presentation] Effect of nucleoporin-related fusion proteins found in leukemia on NF-κB pathway (2013)
  • Author(s): Cigdem Sadik、齋藤 祥子、永田 恭介
  • Organizer: 平成25年度日本生化学会関東支部例会
  • Place of Presentation: 山梨
• [Presentation] 細胞がん化に関わる核膜孔タンパク質の発現異常 (2012)
  • Author(s): 齋藤祥子、Cigdem Sadik、永田恭介
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡