title: Choice of biological source material supersedes oxidative stress in its influence on DJ-1 in vivo interactions with Hsp90.
abstract: DJ-1 is a small but relatively abundant protein of unknown function that may undergo stress-dependent cellular translocation and has been implicated in both neurodegenerative diseases and cancer. As such, DJ-1 may be an excellent study object to elucidate the relative influence of the cellular context on its interactome and for exploring whether acute exposure to oxidative stressors alters its molecular environment. Using quantitative mass spectrometry, we conducted comparative DJ-1 interactome analyses from in vivo cross-linked brains or livers and from hydrogen peroxide-treated or naïve embryonic stem cells. The analysis identified a subset of glycolytic enzymes, heat shock proteins 70 and 90, and peroxiredoxins as interactors of DJ-1. Consistent with a role of DJ-1 in Hsp90 chaperone biology, we document destabilization of Hsp90 clients in DJ-1 knockout cells. We further demonstrate the existence of a C106 sulfinic acid modification within DJ-1 and thereby establish that this previously inferred modification also exists in vivo. Our data suggest that caution has to be exerted in interpreting interactome data obtained from a single biological source material and identify a role of DJ-1 as an oxidative stress sensor and partner of a molecular machinery notorious for its involvement in cell fate decisions.
authors.affiliation: Campbell Family Institute for Breast Cancer Research , Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 2C1, Canada.
authors.forename: Christiane B
authors.initials: CB
authors.lastname: Knobbe
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Revett
authors.forename: Yu
authors.initials: Y
authors.lastname: Bai
authors.forename: Vinca
authors.initials: V
authors.lastname: Chow
authors.forename: Amy Hye Won
authors.initials: AH
authors.lastname: Jeon
authors.forename: Christopher
authors.initials: C
authors.lastname: Böhm
authors.forename: Sepehr
authors.initials: S
authors.lastname: Ehsani
authors.forename: Thomas
authors.initials: T
authors.lastname: Kislinger
authors.forename: Howard T
authors.initials: HT
authors.lastname: Mount
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.forename: Peter
authors.initials: P
authors.lastname: St George-Hyslop
authors.forename: Gerold
authors.initials: G
authors.lastname: Schmitt-Ulms
mesh_terms: D000818:Animals; D003545:Cysteine / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000737:chemistry; D000071617:Protein Deglycase DJ-1; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D013441:Sulfinic Acids / Q000737:chemistry
chemical_list: D050883:HSC70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D020543:Proteome; D013441:Sulfinic Acids; D054464:Peroxiredoxins; C105131:PARK7 protein, human; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1; D003545:Cysteine