“
“The p53 transcription factor is involved in cell

cycle, apoptosis and differentiation. However, the mechanism of p53 mediated differentiation is not fully understood. Here, we show that recently discovered dual oxidase maturation factor 1 (DUOXA1), which was implicated in neuronal differentiation, CHIR-99021 molecular weight is regulated by p53 and may be an important factor in neuronal differentiation. We show that DUOXA1 is highly expressed in mouse neuronal stem cells with intensive nuclear localization. A strong interaction between DUOXA1 and p53 is observed in undifferentiated cells and declines in terminally differentiated neurons. Overexpressed p53 induces marked DUOXA1 expression in P19 cells and intensifies neuronal differentiation in the presence of retinoic acid, which suggests that p53 and DUOXA1 possess a neural differentiation potential. At day 3 of retinoic acid induced differentiation when cells showed a typical morphology of neuronal progenies, CD133 expression was down-regulated. The expression Selleck Flavopiridol level of CD133 was significantly decreased in p53 over-expressing cells and was accompanied by a substantial increase in the expression level of neurofilament. In conclusion, DUOXA1 is a novel p53-regulated neurogenic factor involved in p53 dependent neuronal differentiation. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“The promyelocytic

leukemia (PML) protein is expressed in the diffuse nuclear fraction of the nucleoplasm and in matrix-associated structures, known as nuclear bodies (NBs). PML NB formation requires the covalent modification of PML to SUMO. The noncovalent interactions of SUMO with PML based on the identification of a SUMO-interacting motif within PML seem to be required for further recruitment within PML NBs of SUMOylated proteins. RNA viruses whose replication takes place in the cytoplasm and is inhibited by PML have developed various strategies to counteract the antiviral defense mediated by PML NBs. We show here that primary fibroblasts derived from PML knockout mice are more 10058-F4 mouse sensitive to infection

with encephalomyocarditis virus (EMCV), suggesting that the absence of PML results in an increase in EMCV replication. Also, we found that EMCV induces a decrease in PML protein levels both in interferon-treated cells and in PMLIII-expressing cells. Reduction of PML was carried out by the EMCV 3C protease. Indeed, at early times postinfection, EMCV induced PML transfer from the nucleoplasm to the nuclear matrix and PML conjugation to SUMO-1, SUMO-2, and SUMO-3, leading to an increase in PML body size where the viral protease 3C and the proteasome component were found colocalizing with PML within the NBs. This process was followed by PML degradation occurring in a proteasome-and SUMO-dependent manner and did not involve the SUMO-interacting motif of PML.