酸化ストレス応答に着目したデータベース「Localizatome」を開発~8,000種超のタンパク質局在変化を網羅的解析、老化・がんなどの研究や創薬に貢献~

ad

2025-05-12 東京科学大学

東京科学大学を中心とした研究グループは、酸化ストレス下でのタンパク質の細胞内局在変化を網羅的に解析し、世界初のデータベース「Localizatome」を開発しました。独自のハイスループット顕微鏡と機械学習を活用し、8,055種類のヒトタンパク質の局在データを収集。1,910種が酸化ストレス依存で集積体を形成することを発見し、特定のアミノ酸配列モチーフも同定しました。この成果は老化やがんなどの疾患理解や創薬に貢献が期待されます。

酸化ストレス応答に着目したデータベース「Localizatome」を開発~8,000種超のタンパク質局在変化を網羅的解析、老化・がんなどの研究や創薬に貢献~図1. Localizatome(ローカラゼトーム)データベース概要

<関連情報>

タンパク質におけるストレス依存的な細胞内局在変化のデータベースLocalizatome Localizatome: a database for stress-dependent subcellular localization changes in proteins

Takahide Matsushima , Yuki Naito , Tomoki Chiba , Ryota Kurimoto , Keiko Itano , Koji Ochiai , Koichi Takahashi , Naoki Goshima , Hiroshi Asahara
Database  Published:21 April 2025
DOI:https://doi.org/10.1093/database/baaf028

Abstract

Understanding protein subcellular localization and its dynamic changes is crucial for elucidating cellular function and disease mechanisms, particularly under stress conditions, where protein localization changes can modulate cellular responses. Currently available databases provide insights into protein localization under steady-state conditions; however, stress-related dynamic localization changes remain poorly understood. Here, we present the Localizatome, a comprehensive database that captures stress-induced protein localization dynamics in living cells. Using an original high-throughput microscopy system and machine learning algorithms, we analysed the localization patterns of 10 287 fluorescent protein-fused human proteins in HeLa cells before and after exposure to oxidative stress. Our analysis revealed that 1910 proteins exhibited oxidative stress-dependent localization changes, particularly forming distinct foci. Among them, there were stress granule assembly factors and autophagy-related proteins, as well as components of various signalling pathways. Subsequent characterization identified some specific amino acid motifs and intrinsically disordered regions associated with stress-induced protein redistribution. The Localizatome provides open access to these data through a web-based interface, supporting a wide range of studies on cellular stress response and disease mechanisms.

医療・健康
ad
ad
Follow
ad
タイトルとURLをコピーしました