Molecular mechanism of tumorigenesis related to aberrant nuclear-cytoplasmic transport

2014 Fiscal Year Final Research Report

• 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
• 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

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.

Free Research Field

細胞生物学