Integrated stress response
Integrated Stress Response (ISR)[1] is a cellular stress response common to all eukaryotes. ISR is a common denominator of different types of cellular stresses resulting in activation of at least one of the eIF-2 alpha (EIF2S1).
ISR results in the:
- Down regulation of the general protein synthesis (CAP-dependent)
- Up regulation of translation and expression of certain transcription factors, e.g. Activating Transcription Factor 4 (ATF4)
Pathways that activate eIF-2 alpha include:
- mTOR pathway induced by insufficient glucose and other nutrients.
- unfolded protein response induced by unfolded proteins in the endoplasmic reticulum.
- Amino acid response Pathway induced by insufficient amino acids.
- Protein kinase R stress pathway induced by dsRNA (indicative of a potential viral infection).
- Heme-regulated inhibitor kinase pathway induced in response to oxidative stress, heme deficiency, osmotic shock and heat shock.
See also endoplasmic reticulum stress and the unfolded protein response.
References
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