2013 Fiscal Year Final Research Report

RBM5 plays important roles in the post-transcriptional regulation of mRNAs that are involved in the metabolism of chemotherapeutic reagents.

Research Project

Project/Area Number	23591007
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Gastroenterology
Research Institution	Hokkaido University
Principal Investigator	KAWAKAMI Hiroshi 北海道大学, 大学病院, 助教 (80399823)
Co-Investigator(Kenkyū-buntansha)	KOBAYASHI Takahiko 北海道大学, 大学院医学研究科, 客員研究員 (80333607)
Project Period (FY)	2011 – 2013
Keywords	薬剤耐性
Research Abstract	Despite recent advances in various chemotherapeutic regimens, pancreatic cancer remains highly resistant to conventional chemotherapy. The putative tunor suppressor RBM5 is known to modulate apoptosis and cell cycle arrest but the molecular mechanisms of RBM5 function are poorly understood. We show here that RBM5 interacted with HuR, which is one of mRNA regulatory proteins that bind AU-rich elements in the 3'-untranslated regions of target mRNAs, stabilizing them and modulating their translation. Certain cell stresses including chemotherapeutic reagents induce translocation of HuR from the nucleus to the cytoplasm. RBM5 associated with HuR in the nucleus and reduced translocation of HuR to the cytoplasm. Furthermore, RBM5 overexpression decreased the association of HuR with target mRNAs. Taken together, we suggest that RBM5 might play important roles in the post-transcriptional regulation of mRNAs that are involved in the metabolism of chemotherapeutic reagents.