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C-mannosylation基質タンパク質の細胞生物学的解析 (本文)

水田, 隼斗 慶應義塾大学

2022.09.05

概要

ヒトゲノムプロジェクトの完了と共に幕開けしたポストゲノム時代において、遺伝子レベル、タンパク質レベルの大規模解析が次々と実施されてきた。しかし未だに生命現象は多くの謎に包まれている。この要因の1つとして糖鎖修飾があげられる。糖鎖は核酸、タンパク質に次ぐ第3の生命鎖と位置付けられており、あらゆる生命現象に関与していることが知られている。一方、糖鎖修飾の中でもC-mannosylationは発見から約25年が経過した現在も、その基質タンパク質の報告例が他の糖鎖修飾と比較して顕著に少ない。そのため本修飾がタンパク質、さらには細胞、個体へ与える影響に関しては未解明な点が多い。そこで本研究では、コンセンサス配列を満たすRspo2、RAMP1、ANGPTL4の3つのタンパク質に注目し、それぞれC-mannosylationされるのか否か、そしてされた場合の機能を解明することを目的とした。それぞれRspo2はWnt/β-catenin経路、RAMP1はGPCRを介したシグナル経路、ANGPTL4は腫瘍細胞の転移などと深く関わりがあり、いずれも本邦における死因第1位であるがんとの関連性が高い。したがって、C-mannosylationの有無や機能解析により基質タンパク質へ与える影響を明らかにし、C-mannosylationそのものに対する理解を深めることが、新規がん治療法の開発やバイオマーカーにつながると期待する。

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