Abstract
Snf1, a member of the AMP-activated protein kinase family, plays a critical role in metabolic energy control in yeast cells. Snf1 activity is activated by phosphorylation of Thr-210 on the activation loop of its catalytic subunit; following activation, Snf1 regulates stress-responsive transcription factors. Here, we report that the level of Snf1 protein is dramatically decreased in a UBP8- and UBP10-deleted yeast mutant (ubp8Δ ubp10Δ), and this is independent of transcriptional regulation and proteasome-mediated degradation. Surprisingly, most Snf1-mediated functions, including glucose limitation regulation, utilization of alternative carbon sources, stress responses, and aging, are unaffected in this strain. Snf1 phosphorylation in ubp8Δ ubp10Δ cells is hyperactivated upon stress, which may compensate for the loss of the Snf1 protein and protect cells against stress and aging. Furthermore, artificial elevation of Snf1 phosphorylation (accomplished through deletion of REG1, which encodes a protein that regulates Snf1 dephosphorylation) restored Snf1 protein levels and the regulation of Snf1 activity in ubp8Δ ubp10Δ cells. Our results reveal the existence of a feedback loop that controls Snf1 protein level and its phosphorylation, which is masked by Ubp8 and Ubp10 through an unknown mechanism. We propose that this dynamic modulation of Snf1 phosphorylation and its protein level may be important for adaptation to environmental stress.
Highlights
Snf1/AMPK activity plays a vital role in adaptation to environmental stress
Our findings reveal the existence of a feedback loop between Snf1 protein level and its phosphorylation status, which acts to fine-tune the activity of Snf1 for adaptation to environmental stress
This implied that the reduction of Snf1 protein level in ubp8⌬ ubp10⌬ cells may be due to post-transcriptional regulation or translational control
Summary
Snf1/AMPK activity plays a vital role in adaptation to environmental stress. Results: Elevation of Snf phosphorylation restores Snf protein in a mutant with low Snf levels. Our results reveal the existence of a feedback loop that controls Snf protein level and its phosphorylation, which is masked by Ubp and Ubp through an unknown mechanism We propose that this dynamic modulation of Snf phosphorylation and its protein level may be important for adaptation to environmental stress. SNF1 protein kinase plays a key role in adaptation of yeast cells to glucose limitation and utilization of alternative carbon sources, which occurs through activation of Snf via phosphorylation of Thr-210 on the activation loop of the catalytic subunit by upstream kinases (Sak, Tos, and Elm1) (8 –10); the Reg1-Glc and Sit phosphatases reverse this modification [11,12,13]. Our findings reveal the existence of a feedback loop between Snf protein level and its phosphorylation status, which acts to fine-tune the activity of Snf for adaptation to environmental stress
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