Characterization of the esophageal carcinogenesis-promoting molecular switch existing inside the isoform of RNA-binding protein

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15618
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: The University of Tokushima
• Principal Investigator: IMOTO Issei 徳島大学, 大学院医歯薬学研究部(医学系), 教授 (30258610)
• Co-Investigator(Renkei-kenkyūsha): MASUDA Kiyoshi 徳島大学, 大学院医歯薬学研究部, 准教授 (00457318) ; OTSUJI Eigo 京都府立医科大学, 医学(系)研究科, 教授 (20244600) ; TANGOKU Akira 徳島大学, 大学院医歯薬学研究部, 教授 (10197593)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: RNA結合蛋白 / TIA1 / アイソフォーム / 天然変性領域 / 蛋白リン酸化 / 癌促進作用 / 細胞内局在 / 分子スイッチ

Outline of Final Research Achievements

TIA1a is the isoform of TIA1, one of the RNA-binding protein (RBP), having a serine/threonine-rich intrinsically disordered region (IDR) and promoting esophageal squamous cell carcinoma (ESCC). Through changing amino acid of candidate phosphorylation sites around the TIA1a specific region within IDR, subcellular localization of TIA1a and cell growth were altered in ESCC cells. Blocking synthetic peptides inhibited TIA1a cytoplasmic localization. CHK1 was identified as candidate kinase contributing to TIA1a cytoplasmic localization. In addition, TIA1a bound 3'UTR of candidate TIA1a-binding mRNAs in the cytoplasm with other RBPs and regulated mRNA/protein levels of those targets jointly or competitively. These results demonstrated that the phosphorylation of specific sites within IDR may work as a molecular switch to promote cytoplasmic localization of TIA1a and accelerate its cancer-promoting function through binding and regulating target molecules in the cytoplasm of ESCC cells.

Free Research Field

ゲノム医科学