title: The FOX transcription factor Hcm1 regulates oxidative metabolism in response to early nutrient limitation in yeast. Role of Snf1 and Tor1/Sch9 kinases.
abstract: Within Saccharomyces cerevisiae, Hcm1is a member of the forkhead transcription factor family with a role in chromosome organization. Our group recently described its involvement in mitochondrial biogenesis and stress resistance, and reports here that Hcm1 played a role in adaptation to respiratory metabolism when glucose or nitrogen was decreased. Regulation of Hcm1 activity occurs in at least three ways: i) protein quantity, ii) subcellular localization, and iii) transcriptional activity. Transcriptional activity was measured using a reporter gene fused to a promoter that contains a binding site for Hcm1. We also analyzed the levels of several genes whose expression is known to be regulated by Hcm1 levels and the role of the main kinases known to respond to nutrients. Lack of sucrose-nonfermenting (Snf1) kinase increases cytoplasmic localization of Hcm1, whereas Δtor1 cells showed a mild increase in nuclear Hcm1. In vitro experiments showed that Snf1 clearly phosphorylates Hcm1 while Sch9 exerts a milder phosphorylation. Although in vitroTor1 does not directly phosphorylate Hcm1, in vivo rapamycin treatment increases nuclear Hcm1. We conclude that Hcm1 participates in the adaptation of cells from fermentation to respiratory metabolism during nutrient scarcity. According to our hypothesis, when nutrient levels decrease, Snf1 phosphorylates Hcm1. This results in a shift from the cytoplasm to the nucleus and increased transcriptional activity of genes involved in respiration, use of alternative energy sources, NAD synthesis and oxidative stress resistance.
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, Lleida, Catalonia, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Rodríguez-Colman
authors.forename: M Alba
authors.initials: MA
authors.lastname: Sorolla
authors.forename: Núria
authors.initials: N
authors.lastname: Vall-Llaura
authors.forename: Jordi
authors.initials: J
authors.lastname: Tamarit
authors.forename: Joaquim
authors.initials: J
authors.lastname: Ros
authors.forename: Elisa
authors.initials: E
authors.lastname: Cabiscol
mesh_terms: D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D005502:Food; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013395:Sucrose / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D051858:Forkhead Transcription Factors; D005947:Glucose; D009584:Nitrogen; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; D013395:Sucrose; C079874:HCM1 protein, S cerevisiae; C071570:SNF1-related protein kinases; C083324:TOR1 protein, S cerevisiae; C530964:SCH9 protein, S cerevisiae