Multiple system-level feedback loops control life-and-death decisions in endoplasmic reticulum stress

FEBS Letters

article

Orsolya Kapuy¹  Margita Márton¹  Gábor Bánhegyi¹  P. K. Vinod³ 

[1] Department of Medical Chemistry, Semmelweis University;Pathobiochemistry Research Group of the Hungarian Academy of Sciences and Semmelweis University;Centre for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology

关键词: autophagy;    apoptosis;    endoplasmic reticulum stress;    systems biology;    feedback loops;   

DOI  :  10.1002/1873-3468.13689

来源: John Wiley & Sons Ltd.

【 摘 要 】

Scientific results have revealed that autophagy is able to promote cell survival in response to endoplasmic reticulum (ER) stress, while drastic events result in apoptotic cell death. Here, we analyse the important crosstalk of life-and-death decisions from a systems biological perspective by studying the regulatory modules of the unfolded protein response (UPR). While a double-negative loop between autophagy and apoptosis inducers is crucial for the switch-like characteristic of the stress response mechanism, a positive feedback loop between ER stress sensors is also essential. Corresponding to experimental data, here, we show the dynamical significance of Gadd34-CHOP connections inside the PERK branch of the UPR. The multiple system-level feedback loops seem to be crucial for managing a robust life-and-death decision depending on the level and durability of cellular stress.

【 授权许可】

Unknown