title: Roles of Ca2+ ions in the control of ChREBP nuclear translocation.
abstract: Carbohydrate-responsive element binding protein (ChREBP (MLXIPL)) is emerging as an important mediator of glucotoxity both in the liver and in the pancreatic β-cells. Although the regulation of its nuclear translocation and transcriptional activation by glucose has been the subject of intensive research, it is still not fully understood. We have recently uncovered a novel mechanism in the excitable pancreatic β-cell where ChREBP interacts with sorcin, a penta-EF-hand Ca(2)(+)-binding protein, and is sequestered in the cytosol at low glucose concentrations. Upon stimulation with glucose and activation of Ca(2)(+) influx, or application of ATP as an intracellular Ca(2)(+)-mobilising agent, ChREBP rapidly translocates to the nucleus. In sorcin-silenced cells, ChREBP is constitutively present in the nucleus, and both glucose and Ca(2)(+) are ineffective in stimulating further ChREBP nuclear shuttling. Whether an active Ca(2)(+)-sorcin element of ChREBP activation also exists in non-excitable cells is discussed.
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Section of Cell Biology, Department of Medicine, Imperial College London, SW7 2AZ London, UK. i.leclerc@imperial.ac.uk
authors.forename: Isabelle
authors.initials: I
authors.lastname: Leclerc
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rutter
authors.forename: Gargi
authors.initials: G
authors.lastname: Meur
authors.forename: Nafeesa
authors.initials: N
authors.lastname: Noordeen
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002413:Cations, Divalent / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005947:Glucose / Q000502:physiology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism; D021381:Protein Transport
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002135:Calcium-Binding Proteins; D002413:Cations, Divalent; C116385:MLXIPL protein, human; C503113:SRI protein, human; D005947:Glucose; D002118:Calcium