Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study investigated mRNA expression profiles of bovine oocytes and blastocysts by using a cross-species hybridization approach employing an array consisting of 15,529 human cDNAs as probe, thus enabling the identification of conserved genes during human and bovine preimplantation development. Our analysis revealed 419 genes that were expressed in both oocytes and blastocysts. The expression of 1,324 genes was detected exclusively in the blastocyst, in contrast to 164 in the oocyte including a significant number of novel genes. Genes indicative for transcriptional and translational control (ELAVL4, TACC3) were overexpressed in the oocyte, whereas cellular trafficking (SLC2A14, SLC1A3), proteasome (PSMA1, PSMB3), cell cycle (BUB3, CCNE1, GSPT1), and protein modification and turnover (TNK1, UBE3A) genes were found to be overexpressed in blastocysts. Transcripts implicated in chromatin remodeling were found in both oocytes (NASP, SMARCA2) and blastocysts (H2AFY, HDAC7A). The trophectodermal markers PSG2 and KRT18 were enriched 5- and 50-fold in the blastocyst. Pathway analysis revealed differential expression of genes involved in 107 distinct signaling and metabolic pathways. For example, phosphatidylinositol signaling and gluconeogenesis were prominent pathways identified in the blastocyst. Expression patterns in bovine and human blastocysts were to a large extent identical. This analysis compared the transcriptomes of bovine oocytes and blastocysts and provides a solid foundation for future studies on the first major differentiation events in blastocysts and identification of a set of markers indicative for regular mammalian development.
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PMID:Conserved molecular portraits of bovine and human blastocysts as a consequence of the transition from maternal to embryonic control of gene expression. 1759 43

Histone deacetylase (HDAC) 7 is a member of the HDAC family of deacetylases. Although some of the HDAC proteins have been shown to regulate neuronal survival and death, whether HDAC7 has a similar role is not known. In this study, we show that HDAC7 protects neurons from apoptosis. In cerebellar granule neurons (CGNs) primed to undergo apoptosis by low potassium treatment, expression of HDAC7 protein is reduced. Reduced expression is also observed in CGNs induced to die by pharmacological inhibition of the proteasome, in cortical neurons treated with homocysteic acid, and in the striatum of R6/2 transgenic mice, a commonly used genetic model of Huntington disease. Forced expression of HDAC7 in cultured CGNs blocks low potassium-induced death, and shRNA-mediated suppression of its expression induces death in otherwise healthy neurons. HDAC7-mediated neuroprotection does not require its catalytic domain and cannot be inhibited by chemical inhibitors of HDACs. Moreover, pharmacological inhibitors of the PI3K-Akt or Raf-MEK-ERK signaling pathways or that of PKA, PKC, and Ca(2+)/calmodulin-dependent protein kinase fail to reduce neuroprotection by HDAC7. We show that stimulation of c-jun expression, an essential feature of neuronal death, is prevented by HDAC7. shRNA-mediated suppression of HDAC7 expression leads to an increase in c-jun expression. Inhibition of c-jun expression by HDAC7 is mediated at the transcriptional level by its direct association with the c-jun gene promoter. Taken together, our results indicate that HDAC7 is a neuroprotective protein acting by a mechanism that is independent of its deacetylase activity but involving the inhibition of c-jun expression.
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PMID:Neuroprotection by histone deacetylase-7 (HDAC7) occurs by inhibition of c-jun expression through a deacetylase-independent mechanism. 2111 17