title: Feedback Control of Snf1 Protein and Its Phosphorylation Is Necessary for Adaptation to Environmental Stress.
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.
authors.affiliation: From the Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taipei, Taiwan.
authors.forename: Hsiang-En
authors.initials: HE
authors.lastname: Hsu
authors.affiliation: the Institute of Food Science and Technology, College of Bio-Resources and Agriculture, National Taiwan University, Taipei 10617.
authors.forename: Tzu-Ning
authors.initials: TN
authors.lastname: Liu
authors.affiliation: the Institute of Biochemistry and Molecular Biology, National Yang Ming University, Taipei 11221, and the Genomics Research Center and.
authors.forename: Chung-Shu
authors.initials: CS
authors.lastname: Yeh
authors.affiliation: the Institute of Biochemistry and Molecular Biology, National Yang Ming University, Taipei 11221, and the Genomics Research Center and.
authors.forename: Tien-Hsien
authors.initials: TH
authors.lastname: Chang
authors.affiliation: the Institute of Food Science and Technology, College of Bio-Resources and Agriculture, National Taiwan University, Taipei 10617, loyichen@ntu.edu.tw.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Lo
authors.affiliation: From the Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taipei, Taiwan ckao@gate.sinica.edu.tw.
authors.forename: Cheng-Fu
authors.initials: CF
authors.lastname: Kao
mesh_terms: D000220:Adaptation, Biological; D025461:Feedback, Physiological; D015966:Gene Expression Regulation, Fungal; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000502:physiology
chemical_list: C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases
keywords: AMP-activated kinase (AMPK); Reg1; Snf1; Thr-210 phosphorylation; Ubp10; Ubp8; metabolism; protein phosphorylation; signal transduction; stress