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Cardiff, United Kingdom

Tediose T.,Immunity and Biochemistry | Kolev M.,Immunity and Biochemistry | Sivasankar B.,Singapore Institute for Clinical science | Brennan P.,Immunity and Biochemistry | And 3 more authors.
Nucleic Acids Research

Non-malignant cells can be transformed via the activation of kinases that control degradation of neuralrestrictive silencer factor (REST). Here, we identify a mechanism that contributes to the activation of genes, expression of which is controlled by responsive elements containing overlapping binding sites for REST and nucleolin. We demonstrate that both phosphorylated and non-phosphorylated nucleolinbound DNA; however, only phosphorylated nucleolin successfully competed with either full-length REST or a REST-derived DNA-binding peptide, REST68, for binding to the overlapping binding sites. We show that this interplay between the two transcription factors regulates the activation of cell survival and immunomodulatory genes in tumors and non-malignant cells with activated protein kinase C, which is accompanied with alterations in cell proliferation and apoptosis. We propose a model for the regulation of these genes, which brings a new insight into the molecular mechanisms that control cellular transformation driven by activation of protein kinases. © The Author(s) 2010. Source

Heurich B.,Immunity and Biochemistry | Donev R.M.,Immunity and Biochemistry | Petri S.,Hannover Medical School | Claus P.,Hannover Medical School | And 2 more authors.
Journal of Neuroimmunology

Complement activation products are elevated in cerebrospinal fluid, spinal cord and motor cortex of patients with amyotrophic lateral sclerosis (ALS) but are untested in models. We determined complement expression and activation in the SOD1 G93A mouse model of familial ALS (fALS). At 126. days, C3 mRNA was upregulated in spinal cord and C3 protein accumulated in astrocytes and motor neurons. C3 activation products C3b/iC3b were localized exclusively on motor neurons. At the neuromuscular junction, deposits of C3b/iC3b and C1q were detected at day 47, before the appearance of clinical symptoms, and remained detectable at symptomatic stage (126. days). Our findings implicate complement in the denervation of the muscle endplate by day 47 and destruction of the neuromuscular junction and spinal neuron loss by day 126 in the SOD1 G93A mouse model of fALS. © 2011 Elsevier B.V. Source

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