title: Nuclear localization of PAPS synthetase 1: a sulfate activation pathway in the nucleus of eukaryotic cells.
abstract: Sulfation is a major modification of many molecules in eukaryotes that is dependent on the enzymatic synthesis of an activated sulfate donor, 3'-phosphoadenosine 5'-phosphosulfate (PAPS). While sulfate activation has long been assumed to occur in the cytosol, we show in this study that human PAPS synthetase 1 (PAPSS1), a bifunctional ATP sulfurylase/adenosine 5'-phosphosulfate (APS) kinase enzyme sufficient for PAPS synthesis, accumulates in the nucleus of mammalian cells. Nuclear targeting of the enzyme is mediated by its APS kinase domain and requires a catalytically dispensable 21 amino acid sequence at the amino terminus. Human PAPSS1 and Drosophila melanogaster PAPSS localize to the nucleus in yeast and relieve the methionine auxotrophy of ATP sulfurylase- or APS kinase-deficient strains, suggesting that PAPSS1 is fully functional in vivo when targeted to the nucleus. A second PAPS synthetase gene, designated PAPSS2, has recently been described, mutations of which are responsible for abnormal skeletal development in human spondyloepimetaphyseal dysplasia and murine brachymorphism. We found that PAPSS2, which localizes to the cytoplasm when ectopically expressed in mammalian cells, is relocated to the nucleus when coexpressed with PAPSS1. Taken together, these results indicate that a sulfation pathway might exist in the nucleus of eukaryotic cells. -Besset, S., Vincourt, J.-B., Amalric, F., Girard, J.-P. Nuclear localization of PAPS synthetase 1: a sulfate activation pathway in the nucleus of eukaryotic cells.
authors.affiliation: Laboratoire de Biologie Vasculaire, Institut de Pharmacologie et de Biologie Structurale du CNRS, 31077 Toulouse Cedex 4, France.
authors.forename: S
authors.initials: S
authors.lastname: Besset
authors.forename: J B
authors.initials: JB
authors.lastname: Vincourt
authors.forename: F
authors.initials: F
authors.lastname: Amalric
authors.forename: J P
authors.initials: JP
authors.lastname: Girard
mesh_terms: D000818:Animals; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004331:Drosophila melanogaster; D005057:Eukaryotic Cells / Q000201:enzymology; D005816:Genetic Complementation Test; D006801:Humans; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency; D013430:Sulfate Adenylyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism*
chemical_list: D009097:Multienzyme Complexes; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D013431:Sulfates; D017853:Phosphotransferases (Alcohol Group Acceptor); C019617:adenylylsulfate kinase; C022322:PAPS synthetase; D013430:Sulfate Adenylyltransferase