study, we further showed that EBNA3C can negatively regulate p53-mediated functions by interacting with its regulatory proteins, the inhibitor of growth family proteins ING4 and ING5, shown to be frequently deregulated in different cancers. Functional mapping revealed that both ING4 and ING5 bound to N-terminal Selinexor domain residues 129 to 200 of EBNA3C, which was previously demonstrated to associate with p53 and is also essential for LCL growth. In addition, we showed that a conserved domain of either ING4 or ING5 bound to both p53 and EBNA3C in a competitive manner, suggesting a potential role for EBNA3C whereby the ING4 or -5/p53 pathway is modulated in EBV-infected cells. Subsequently, we demonstrated that EBNA3C significantly suppresses both the ING4- and ING5-mediated regulation of p53 transcriptional LY3039478 price activity in a dose-dependent manner. A colony formation assay as well as an apoptosis assay showed that EBNA3C nullified the negative regulatory effects on cell proliferation induced by coupled expression of p53 in the presence of either
ING4 or ING5 in Saos-2 (p53(-/-)) cells. This report demonstrates a possible role for the candidate tumor suppressor ING genes in the biology of EBV-associated cancers.”
“Previous studies have shown an excitatory effect of histamine on neurons in two Cyclin-dependent kinase 3 cerebellar nuclei, the fastigial nucleus and the interposed nucleus. Here we investigated action of histamine on the dentate nucleus (DN), another nucleus of the cerebellum, and provided more evidence for motor control by histamine via the cerebellum. Spontaneous unitary discharge of neurons in the DN was extracellularly recorded by use of cerebellar slice preparations. In total 79-recorded neurons, which were from 53 cerebellar slices, 67 neurons (84.8%) had an excitatory response to histamine stimulation, and the rest (15.2%) were not reactive. The histamine-induced
excitation of the DN neurons was not blocked by low-Ca2+/high-Mg2+ medium, demonstrating that this effect of histamine was postsynaptic. Triprolidine, an antagonist of histamine H-1 receptors, did not block the excitatory effect of histamine, but ranitidine, an antagonist for H-2 receptors, blocked the excitatory response to histamine in a concentration-dependent manner. Further, histamine H-1 receptor agonist 2-pyridylethylamine did not elicit any response of DN neurons, but H-2 receptor agonist dimaprit had an excitatory action on the DN cells and this action was blocked by ranitidine. These results indicate that histamine excites cerebellar DN neurons via histamine H-2 receptors.