title: Hexokinase 2 Is an Intracellular Glucose Sensor of Yeast Cells That Maintains the Structure and Activity of Mig1 Protein Repressor Complex.
abstract: Hexokinase 2 (Hxk2) fromSaccharomyces cerevisiaeis a bi-functional enzyme, being both a catalyst in the cytosol and an important regulator of the glucose repression signal in the nucleus. Despite considerable recent progress, little is known about the regulatory mechanism that controls nuclear Hxk2 association with theSUC2promoter chromatin and how this association is necessary forSUC2gene repression. Our data indicate that in theSUC2promoter context, Hxk2 functions through a variety of structurally unrelated factors, mainly the DNA-binding Mig1 and Mig2 repressors and the regulatory Snf1 and Reg1 factors. Hxk2 sustains the repressor complex architecture maintaining transcriptional repression at theSUC2gene. Using chromatin immunoprecipitation assays, we discovered that the Hxk2 in its open configuration, at low glucose conditions, leaves the repressor complex that induces its dissociation and promotesSUC2gene expression. In high glucose conditions, Hxk2 adopts a close conformation that promotes Hxk2 binding to the Mig1 protein and the reassembly of theSUC2repressor complex. Additional findings highlight the possibility that Hxk2 constitutes an intracellular glucose sensor that operates by changing its conformation in response to cytoplasmic glucose levels that regulate its interaction with Mig1 and thus its recruitment to the repressor complex of theSUC2promoter. Thus, our data indicate that Hxk2 is more intimately involved in gene regulation than previously thought.
authors: From the Department of Biochemistry and Molecular Biology, University of Oviedo, 33006-Oviedo, Spain.
authors: Montserrat
authors: M
authors: Vega
authors: From the Department of Biochemistry and Molecular Biology, University of Oviedo, 33006-Oviedo, Spain.
authors: Alberto
authors: A
authors: Riera
authors: From the Department of Biochemistry and Molecular Biology, University of Oviedo, 33006-Oviedo, Spain.
authors: Alejandra
authors: A
authors: Fernández-Cid
authors: From the Department of Biochemistry and Molecular Biology, University of Oviedo, 33006-Oviedo, Spain.
authors: Pilar
authors: P
authors: Herrero
authors: From the Department of Biochemistry and Molecular Biology, University of Oviedo, 33006-Oviedo, Spain fmoreno@uniovi.es.
authors: Fernando
authors: F
authors: Moreno
mesh_terms: D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D043324:beta-Fructofuranosidase / Q000096:biosynthesis / Q000235:genetics
chemical_list: C085976:MIG1 protein, S cerevisiae; D046912:Multiprotein Complexes; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C071570:SNF1-related protein kinases; C490214:HXK2 protein, S cerevisiae; D006593:Hexokinase; D017346:Protein Serine-Threonine Kinases; D054645:Protein Phosphatase 1; C070829:REG1 protein, S cerevisiae; C468437:SUC2 protein, S cerevisiae; D043324:beta-Fructofuranosidase; D005947:Glucose
keywords: Saccharomyces cerevisiae; gene expression; glucose; glucose signaling; hexokinase; repressor protein