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The clinicopathological phenotype of the Gerstmann-Sträussler-Scheinker disease (GSS) variant linked to the codon 102 mutation in the prion protein (PrP) gene (GSS P102L) shows a high heterogeneity. This variability also is observed in subjects with the same prion protein gene PRNP haplotype and is independent from the duration of the disease. Immunoblot(More)
Interferons (IFNs) regulate diverse cellular functions through activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Lack of Ubp43, an IFN-inducible ISG15 deconjugating enzyme, leads to IFN hypersensitivity in ubp43-/- mice, suggesting an important function of Ubp43 in downregulation of IFN responses. Here, we(More)
Prion diseases are characterized by the presence of the abnormal prion protein PrP(Sc), which is believed to be generated by the conversion of the alpha-helical structure that predominates in the normal PrP isoform into a beta-sheet structure resistant to proteinase K (PK). In human prion diseases, two major types of PrP(Sc), type 1 and 2, can be(More)
BACKGROUND The increase of the 14-3-3 protein in CSF is used as a diagnostic test in Creutzfeldt-Jakob disease (CJD), but the sensitivity and specificity of the 14-3-3 test are disputed. One reason for the dispute may be the recently established heterogeneity of sporadic CJD. The relationship between CSF 14-3-3 protein and sporadic CJD subtypes,(More)
The expression of ubiquitin-like modifier ISG15 and its conjugation to target proteins are highly induced by interferon (IFN) stimulation and during viral and bacterial infections. However, the biological significance of this modification has not been clearly understood. To investigate the function of protein modification by ISG15, we generated a mouse(More)
Nearly every extracellular ligand that has been found to play a role in regulating bone biology acts, at least in part, through MAPK pathways. Nevertheless, much remains to be learned about the contribution of MAPKs to osteoblast biology in vivo. Here we report that the p38 MAPK pathway is required for normal skeletogenesis in mice, as mice with deletion of(More)
The expression of the ubiquitin-like protein ISG15 and protein modification by ISG15 (ISGylation) are strongly activated by interferons. Accordingly, ISG15 expression and protein ISGylation are strongly activated upon viral and bacterial infections and during other stress conditions, suggesting important roles for the ISG15 system in innate immune(More)
Reactive oxygen species (ROS) are supposed to play an important role in hypoxia- and ischemia/reperfusion-mediated neuronal injury with the characteristics of apoptosis. There are many reports showing that cobalt chloride (CoCl(2)) could mimic the hypoxic responses in some aspects including production of ROS in cultured cells. The cytotoxicity of CoCl(2)(More)
Our previous study showed that cobalt chloride (CoCl2) could induce PC12 cell apoptosis and that the CoCl2-treated PC12 cells may serve as a simple in vitro model for the study of the mechanism of hypoxia-linked neuronal disorders. The aim of this study is to elucidate the mechanism of CoCl2-induced apoptosis in PC12 cells. Caspases are known to be involved(More)
Though the interferon-inducible protein ISG15 was one of the first ubiquitin-like modifiers to be discovered, much remains unknown about the identity of proteins conjugated to ISG15 or the biologic consequences of modification. To gain a better understanding of the cellular pathways affected by ISG15, we identified proteins targeted for ISGylation using a(More)