title: Iron-sulphur clusters as genetic regulatory switches: the bifunctional iron regulatory protein-1.
abstract: In the eighties, iron regulatory protein-1 (IRP-1) was identified as a cytoplasmic mRNA-binding protein that regulates vertebrate cell iron metabolism. More recently, IRP-1 was found to represent the functional cytoplasmic homologue of mitochondrial aconitase, a citric acid cycle enzyme. Its two functions are mutually exclusive and depend on the status of an Fe-S cluster: the (cluster-less) apoIRP-1 binds to RNA, while the incorporation of a cubane 4Fe-4S cluster is required for enzymatic activity. Cellular signals including iron levels, nitric oxide and oxidative stress can regulate between the two activities posttranslationally and reversibly via the Fe-S cluster. Recent reports suggest that other regulatory proteins may be controlled by similar mechanisms.
authors.affiliation: Gene Expression Programme, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Paraskeva
authors.forename: M W
authors.initials: MW
authors.lastname: Hentze
mesh_terms: D000154:Aconitate Hydratase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D005786:Gene Expression Regulation; D007501:Iron / Q000378:metabolism*; D035941:Iron Regulatory Protein 1; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000502:physiology*; D005810:Multigene Family; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D013455:Sulfur / Q000378:metabolism*
chemical_list: D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D016601:RNA-Binding Proteins; D013455:Sulfur; D007501:Iron; D000154:Aconitate Hydratase; D035941:Iron Regulatory Protein 1