title: Mutational analyses of the signals involved in the subcellular location of DSCR1.
abstract: BACKGROUND
  Down syndrome is the most frequent genetic disorder in humans. Rare cases involving partial trisomy of chromosome 21 allowed a small chromosomal region common to all carriers, called Down Syndrome Critical Region (DSCR), to be determined. The DSCR1 gene was identified in this region and is expressed preferentially in the brain, heart and skeletal muscle. Recent studies have shown that DSCR1 belongs to a family of proteins that binds and inhibits calcineurin, a serine-threonine phosphatase. The work reported on herein consisted of a study of the subcellular location of DSCR1 and DSCR1-mutated forms by fusion with a green fluorescent protein, using various cell lines, including human.
  
  
  RESULTS
  The protein's location was preferentially nuclear, independently of the isoform, cell line and insertion in the GFP's N- or C-terminal. A segment in the C-terminal, which is important in the location of the protein, was identified by deletion. On the other hand, site-directed mutational analyses have indicated the involvement of some serine and threonine residues in this event.
  
  
  CONCLUSIONS
  In this paper, we discuss the identification of amino acids which can be important for subcellular location of DSCR1. The involvement of residues that are prone to phosphorylation suggests that the location and function of DSCR1 may be regulated by kinases and/or phosphatases.
authors.affiliation: Department of Genetics and Evolution, Federal University of São Carlos, Rodovia Washington Luiz km 235, São Carlos 13565-905, SP, Brazil. scpfister@uol.com.br
authors.forename: Sandra Cristina
authors.initials: SC
authors.lastname: Pfister
authors.forename: Gláucia Maria
authors.initials: GM
authors.lastname: Machado-Santelli
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Han
authors.forename: Flávio
authors.initials: F
authors.lastname: Henrique-Silva
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D016466:CHO Cells / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D019556:COS Cells / Q000737:chemistry; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D016572:Cyclosporine / Q000494:pharmacology; D004268:DNA-Binding Proteins; D004314:Down Syndrome / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015759:Ionomycin / Q000494:pharmacology; D007668:Kidney / Q000737:chemistry / Q000166:cytology / Q000196:embryology; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation / Q000235:genetics; D011392:Proline / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D021382:Protein Sorting Signals / Q000187:drug effects / Q000235:genetics*; D012694:Serine / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013912:Threonine / Q000235:genetics / Q000378:metabolism; D018909:src Homology Domains / Q000235:genetics
chemical_list: D065095:Calcineurin Inhibitors; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D021382:Protein Sorting Signals; C108612:RCAN1 protein, human; D013912:Threonine; D012694:Serine; D015759:Ionomycin; D016572:Cyclosporine; D011392:Proline; D019703:Calcineurin; D013755:Tetradecanoylphorbol Acetate