Cherkasova V, et al. (2010) Snf1 promotes phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 by activating Gcn2 and inhibiting phosphatases Glc7 and Sit4. Mol Cell Biol 30(12):2862-73
Abstract: Snf1 is the ortholog of mammalian AMP-activated kinase, and is responsible for activation of glucose-repressed genes at low glucose levels in budding yeast. We show that Snf1 promotes formation of phosphorylated translation initiation factor eIF2alpha (eIF2[alphaP]), a regulator of general and gene-specific translation, by stimulating the function of eIF2alpha kinase Gcn2 during histidine starvation of glucose-grown cells. Thus, eliminating Snf1 or mutating its activation loop lowers Gcn2 kinase activity, reducing autophosphorylation of Thr-882 in the Gcn2 activation loop, and decreases eIF2(alphaP) levels in starved cells. Consistently, eliminating Reg1, a negative regulator of Snf1, provokes Snf1-dependent hyperphosphorylation of both Thr-882 and eIF2alpha. Interestingly, Snf1 also promotes eIF2alpha phosphorylation in the non-preferred carbon source galactose, but this occurs by inhibition of protein phosphatase 1alpha (Glc7) and the PP2A-like enzyme Sit4, rather than activation of Gcn2. Both Glc7 and Sit4 physically interact with eIF2alpha in cell extracts, supporting their direct roles as eIF2alpha phosphatases. Our results show that Snf1 modulates the level of eIF2alpha phosphorylation by different mechanisms depending on the kind of nutrient deprivation existing in cells.
|Status: Published||Type: Journal Article||PubMed ID: 20404097|
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