ネットワーク構造が作る細胞周期の独立制御―数学が予測した制御モジュールの定量的実証

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2026-09-24 京都大学

京都大学・東京科学大学などの研究グループは、細胞内の反応が複雑なネットワークを形成する中でも、異なる機能を担う反応系を互いに独立して制御できる「緩衝構造」が実際の細胞周期システムに存在することを、数学理論と実験の両面から実証した。研究では、ネットワーク構造から予測された2種類のタンパク質複合体が異なる緩衝構造に属し、一方が変化しても他方が独立して振る舞うことを定量的に確認。さらに、理論から未知の反応を予測し、実験でその存在を検証した。個々の分子を調べるだけでなく、反応ネットワークの構造から生命システムの制御原理を理解するシステム生物学的手法を示した点が重要である。

ネットワーク構造が作る細胞周期の独立制御―数学が予測した制御モジュールの定量的実証
研究全体の概念図

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ネットワークトポロジーが細胞周期システムにおける複数のチェックポイントの独⽴した制御を⽣み出す Network topology creates independent control of multiple checkpoints in the cell cycle system

Yuhei Yamauchi, Hironori Sugiyama, Yuhei Goto, +1 , and Atsushi Mochizuki
Proceedings of the National Academy of Sciences  Published:September 23, 2026
DOI:https://doi.org/10.1073/pnas.2537815123

Abstract

In living cells, numerous chemical reactions are interconnected by sharing substrates and products, forming a huge reaction network. The various functions of cells emerge from the dynamics of such interconnected system. Cells regulate the concentrations of key biochemicals by controlling the amount or activity of enzymes that catalyze each reaction, thereby achieving control of cellular functions. However, in such an interconnected system, can different chemicals responsible for different biological functions be controlled independently? If so, by what mechanism? This paper mathematically demonstrates that “modularity,” where parts of a system are controlled independently of others, arises solely from network topology. Furthermore, using the cell cycle system as an example, we show through a combination of theory and experiments that such “regulatory modules” actually exist in living organisms, performing important roles. In the cell cycle, the G1-S and G2-M transitions are strictly controlled by distinct protein complexes, requiring the specific activation of different complexes at different phases. This suggests that different transitions should be independently controlled. However, two cell-cycle-control complexes share a common protein component, raising the question of how phase-specific control is achieved. Analysis of a known cell cycle network using a topology-based theory revealed that the two complexes belong to different regulatory modules. Experimental verification confirms the existence of a module. Moreover, by comparing theoretical predictions with experimental verification, we theoretically predict the necessity of an unknown reaction and experimentally confirm it. This prediction and verification approach using model-free theory enables the updating of the network information.

生物工学一般
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