title: The Atypical Dual Specificity Phosphatase hYVH1 Associates with Multiple Ribonucleoprotein Particles.
abstract: Human YVH1 (hYVH1), also known as dual specificity phosphatase 12 (DUSP12), is a poorly characterized atypical dual specificity phosphatase widely conserved throughout evolution. Recent findings have demonstrated that hYVH1 expression affects cellular DNA content and is a novel cell survival phosphatase preventing both thermal and oxidative stress-induced cell death, whereas studies in yeast have established YVH1 as a novel 60S ribosome biogenesis factor. In this study, we have isolated novel hYVH1-associating proteins from human U2OS osteosarcoma cells using affinity chromatography coupled to mass spectrometry employing ion mobility separation. Numerous ribosomal proteins were identified, confirming the work done in yeast. Furthermore, proteins known to be present on additional RNP particles were identified, including Y box-binding protein 1 (YB-1) and fragile X mental retardation protein, proteins that function in translational repression and stress granule regulation. Follow-up studies demonstrated that hYVH1 co-localizes with YB-1 and fragile X mental retardation protein on stress granules in response to arsenic treatment. Interestingly, hYVH1-positive stress granules were significantly smaller, whereas knocking down hYVH1 expression attenuated stress granule breakdown during recovery from arsenite stress, indicating a possible role for hYVH1 in stress granule disassembly. These results propagate a role for dual specificity phosphatases at RNP particles and suggest that hYVH1 may affect a variety of fundamental cellular processes by regulating messenger ribonucleoprotein (mRNP) dynamics.
authors.affiliation: From the Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario N9B 3P4, Canada.
authors.forename: Qiudi
authors.initials: Q
authors.lastname: Geng
authors.affiliation: From the Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario N9B 3P4, Canada.
authors.forename: Besa
authors.initials: B
authors.lastname: Xhabija
authors.affiliation: From the Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario N9B 3P4, Canada.
authors.forename: Colleen
authors.initials: C
authors.lastname: Knuckle
authors.affiliation: From the Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario N9B 3P4, Canada.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Bonham
authors.affiliation: From the Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario N9B 3P4, Canada vacratsi@uwindsor.ca.
authors.forename: Panayiotis O
authors.initials: PO
authors.lastname: Vacratsis
mesh_terms: D018053:Arsenites / Q000494:pharmacology; D045744:Cell Line, Tumor; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000378:metabolism*; D054638:Dual Specificity Phosphatase 1 / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D012261:Ribonucleoproteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects; D051840:Y-Box-Binding Protein 1 / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D018053:Arsenites; D012261:Ribonucleoproteins; D012269:Ribosomal Proteins; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; C015001:arsenite
keywords: DUSP12; MS; YVH1; dual specificity phosphoprotein phosphatase; ion mobility; ribonucleoprotein (RNP); stress granule; tyrosine-protein phosphatase (tyrosine phosphatase)