Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Progressive myoclonus epilepsy of Univerricht-Lundborg type is a clinically defined entity among the progressive myoclonus epilepsies. It is an autosomal recessive disorder. The underlying biochemical defect is unknown. We used linkage analysis to localize the gene in 12 families with the aid of polymorphic DNA markers. Close linkage was detected with three markers on distal chromosome 21. The loci BCEI and D21S154 gave the highest positive logarithm-of-odds (lod) scores of 5.49 and 4.25, respectively, at zero recombination. The third locus, D21S112, gave a lod score of 6.91 at a recombination fraction of 0.034. There was no evidence of heterogeneity. Multipoint lod scores calculated against a fixed map of the three marker loci gave a maximum four-point lod score of 10.08 at a location of the disease gene at 6.0 centimorgans distal to locus BCEI and 0.8 centimorgan proximal to locus D21S154. As markers BCEI and D21S154 have previously been localized to 21q22.3 by physical methods, our findings place the EMP1 gene locus (for progressive myoclonus epilepsy of the Unverricht-Lundborg type) in chromosome 21 band q22.3. This finding provides an opportunity to test several other epilepsy phenotypes, particularly the so-called Ramsay Hunt syndrome, for linkage to the same locus. It also is a starting point toward isolating and characterizing the gene and its protein product.
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PMID:Localization of a gene for progressive myoclonus epilepsy to chromosome 21q22. 167 90

Valproate (VPA) and trichostatin A (TSA), inhibitors of zinc-dependent deacetylase activity, induce reduction in the levels of mRNA encoding oestrogen receptor-alpha (ERalpha), resulting in subsequent clearance of ERalpha protein from breast and ovarian cell lines. Inhibition of oestrogen signalling may account for the endocrine disorders, menstrual abnormalities, osteoporosis and weight gain that occur in a proportion of women treated with VPA for epilepsy or for bipolar mood disorder. Transcriptome profiling revealed that VPA and TSA also modulate the expression of, among others, key regulatory components of the cell cycle. Meta-analysis of genes directly responsive to oestrogen indicates that VPA and TSA have a generally antioestrogenic profile in ERalpha positive cells. Concomitant treatment with cycloheximide prevented most of these changes in gene expression, including downregulation of ERalpha mRNA, indicating that a limited number of genes signal a hyperacetylated state within cells. Three members of the NAD-dependent deacetylases, the sirtuins, are upregulated by VPA and by TSA and sirtuin activity contributes to loss of ERalpha expression. However, prolonged inhibition of the sirtuins by sirtinol also induces loss of ERalpha from cells. Mechanistically, we show that VPA invokes reversible promoter shutoff of the ERalpha, pS2 and cyclin D1 promoters, by inducing recruitment of methyl cytosine binding protein 2 (MeCP2) with concomitant exclusion of the maintenance methylase DNMT1. Furthermore, we demonstrate that, in the presence of VPA, local DNA methylation, deacetylation and demethylation of activated histones and recruitment of inhibitory complexes occurs on the pS2 promoter.
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PMID:Multiple mechanisms induce transcriptional silencing of a subset of genes, including oestrogen receptor alpha, in response to deacetylase inhibition by valproic acid and trichostatin A. 1587 Jun 96