Investigation of the medical/biological roles of the parafibromin functions regulated by SHP2 oncoprotein

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K18399
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: The University of Tokyo
• Principal Investigator: TAKAHASHI Atsushi 東京大学, 大学院医学系研究科(医学部), 助教 (00624496)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: Parafibromin / チロシン脱リン酸化酵素SHP2 / Wntシグナル伝達経路 / YAP / 選択的スプライシング

Outline of Final Research Achievements

(1) It was suggested that deregulated tyrosine-dephosphorylation of Parafibromin caused lethal defects in embryogenesis of mice. We reported that tyrosine-dephosphorylated form of Parafibromin acts as a coactivator of the Wnt/Hedgehog/Notch signaling pathways, which play crucial roles in morphogenesis.
(2) Loss of function of the leucine-zipper motif lost the SHP2-binding ability of the YAP isoform that possesses the exon 6-encoded γ-segment. The YAP isoform lacking the γ-segment was incapable in binding to SHP2, collectively indicated that YAP requires the leucine-zipper motif, which is encoded in the exon 5 and 7, for the complex formation with SHP2.

Free Research Field

がん生物学、分子腫瘍学、分子生物学