title: Nuclear import of the yeast hexokinase 2 protein requires α/β-importin-dependent pathway.
abstract: Hexokinase 2 (Hxk2) from Saccharomyces cerevisiae was one of the first metabolic enzymes described as a multifunctional protein. Hxk2 has a double subcellular localization and role, it functions as a glycolytic enzyme in the cytoplasm and as a regulator of gene transcription of several Mig1-regulated genes in the nucleus. However, the mechanism by which Hxk2 enters in the nucleus was unknown until now. Here, we report that the Hxk2 protein is an import substrate of the carriers α-importin (Kap60 in yeast) and β-importin (Kap95 in yeast). We also show that the Hxk2 nuclear import and the binding of Hxk2 with Kap60 are glucose-dependent and involve one lysine-rich nuclear localization sequence (NLS), located between lysine 6 and lysine 12. Moreover, Kap95 facilitates the recognition of the Hxk2 NLS1 motif by Kap60 and both importins are essential for Hxk2 nuclear import. It is also demonstrated that Hxk2 nuclear import and its binding to Kap95 and Kap60 depend on the Gsp1-GTP/GDP protein levels. Thus, our study uncovers Hxk2 as a new cargo for the α/β-importin pathway of S. cerevisiae.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Oviedo, 33006 Oviedo, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Peláez
authors.forename: Paula
authors.initials: P
authors.lastname: Fernández-García
authors.forename: Pilar
authors.initials: P
authors.lastname: Herrero
authors.forename: Fernando
authors.initials: F
authors.lastname: Moreno
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D020816:Amino Acid Motifs; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000235:genetics / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000235:genetics / Q000378:metabolism; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism*; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism*; D028961:beta Karyopherins / Q000235:genetics / Q000378:metabolism*
chemical_list: C080324:GSP1 protein, S cerevisiae; C085976:MIG1 protein, S cerevisiae; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D028901:alpha Karyopherins; D028961:beta Karyopherins; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; C490214:HXK2 protein, S cerevisiae; D006593:Hexokinase; D020559:Monomeric GTP-Binding Proteins