title: Global stress response in a prokaryotic model of DJ-1-associated Parkinsonism.
abstract: YajL is the most closely related Escherichia coli homolog of Parkinsonism-associated protein DJ-1, a protein with a yet-undefined function in the oxidative-stress response. YajL protects cells against oxidative-stress-induced protein aggregation and functions as a covalent chaperone for the thiol proteome, including FeS proteins. To clarify the cellular responses to YajL deficiency, transcriptional profiling of the yajL mutant was performed. Compared to the parental strain, the yajL mutant overexpressed genes coding for chaperones, proteases, chemical chaperone transporters, superoxide dismutases, catalases, peroxidases, components of thioredoxin and glutaredoxin systems, iron transporters, ferritins and FeS cluster biogenesis enzymes, DNA repair proteins, RNA chaperones, and small regulatory RNAs. It also overexpressed the RNA polymerase stress sigma factors sigma S (multiple stresses) and sigma 32 (protein stress) and activated the OxyR and SoxRS oxidative-stress transcriptional regulators, which together trigger the global stress response. The yajL mutant also overexpressed genes involved in septation and adopted a shorter and rounder shape characteristic of stressed bacteria. Biochemical experiments showed that this upregulation of many stress genes resulted in increased expression of stress proteins and improved biochemical function. Thus, protein defects resulting from the yajL mutation trigger the onset of a robust and global stress response in a prokaryotic model of DJ-1-associated Parkinsonism.
authors.affiliation: Stress Molecules, Institut Jacques Monod, Université Paris, Paris, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Messaoudi
authors.forename: Valérie
authors.initials: V
authors.lastname: Gautier
authors.forename: Fatoum
authors.initials: F
authors.lastname: Kthiri
authors.forename: Gaelle
authors.initials: G
authors.lastname: Lelandais
authors.forename: Mouadh
authors.initials: M
authors.lastname: Mihoub
authors.forename: Danièle
authors.initials: D
authors.lastname: Joseleau-Petit
authors.forename: Teresa
authors.initials: T
authors.lastname: Caldas
authors.forename: Chantal
authors.initials: C
authors.lastname: Bohn
authors.forename: Leah
authors.initials: L
authors.lastname: Tolosa
authors.forename: Govind
authors.initials: G
authors.lastname: Rao
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tao
authors.forename: Ahmed
authors.initials: A
authors.lastname: Landoulsi
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouloc
authors.forename: Gilbert
authors.initials: G
authors.lastname: Richarme
mesh_terms: D004260:DNA Repair; D004269:DNA, Bacterial / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000235:genetics; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000235:genetics; D000071617:Protein Deglycase DJ-1; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D015513:Oncogene Proteins; D012269:Ribosomal Proteins; C554198:YajL protein, E coli; D007501:Iron; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1