Phosphorylation of eukaryotic initiation factor-2α (eIF2α) in autophagy.
Abstract
The integrated stress response is characterized by the phosphorylation of eukaryotic initiation factor-2α (eIF2α) on serine 51 by one out of four specific kinases (EIF2AK1 to 4). Here we provide three series of evidence suggesting that macroautophagy (to which we refer to as autophagy) induced by a variety of distinct pharmacological agents generally requires this phosphorylation event. First, the induction of autophagic puncta by various distinct compounds was accompanied by eIF2α phosphorylation on serine 51. Second, the modulation of autophagy by >30 chemically unrelated agents was partially inhibited in cells expressing a non-phosphorylable (S51A) mutant of eIF2α or lacking all four eIF2α kinases, although distinct kinases were involved in the response to different autophagy inducers. Third, inhibition of eIF2α phosphatases was sufficient to stimulate autophagy. In synthesis, it appears that eIF2α phosphorylation is a central event for the stimulation of autophagy.
References
Inhibition of transcription by dactinomycin reveals a new characteristic of immunogenic cell stress.
Citations
Methods Mentioned
Software Mentioned
Related Concepts
Related Feeds
Autophagy & Model Organisms
Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms
Autophagy Networks
Autophagy is a lysosomal pathway that involves degradation of proteins and functions in normal growth and pathological conditions, through a series of complex networks. The catabolic process involves delivery of proteins and organelles to the lysosome. Here is the latest research on autophagy networks.