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Multiple system‐level feedback loops control life‐and‐death decisions in endoplasmic reticulum stress
Author(s) -
Kapuy Orsolya,
Márton Margita,
Bánhegyi Gábor,
Vinod P. K.
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13689
Subject(s) - endoplasmic reticulum , unfolded protein response , autophagy , crosstalk , microbiology and biotechnology , programmed cell death , apoptosis , inducer , negative feedback , mechanism (biology) , biology , chemistry , computer science , physics , biochemistry , voltage , quantum mechanics , gene , optics
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.