Fine Tuning of the UPR by the Ubiquitin Ligases Siah1/2

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Maintaining a balanced level of stress (protein folding, reactive oxygen radicals) is important for keeping cellular homeostasis (the ability of a cell to maintain internal equilibrium by adjusting its physiological processes). The accumulation of stress (external or internal) will trigger a well-orchestrated machinery that attempts to restore homeostasis, namely, the unfolded protein response (UPR). The UPR either restores balance to the cells or induces a cell death program, which clears the damaged cell. How this machinery activates cell survival versus cell death is not entirely clear. Here we identify a new layer in the regulation of the UPR, which determines the magnitude of this response. We demonstrate the importance of this newly identified regulatory component for cell death commitments, in response to the more severe conditions (ischemia, lack of oxygen and nutrients). Our findings highlight an undisclosed mechanism that is important for the cell death decision following severe stress conditions, while pointing to the ability to fine tune cellular response to stress.

Vyšlo v časopise: Fine Tuning of the UPR by the Ubiquitin Ligases Siah1/2. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004348
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004348

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