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Abstract: 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, 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 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. [Copyright &y& Elsevier]

Abstract: Previous reports have shown that metallothionein (MT) may modulate p53 activity through zinc exchange. However, little is known on a direct interaction between MT and p53 in cells. The results demonstrate an interaction between MT and p53 can occur in vitro. The complex between MT and p53 was observed in breast cancer epithelial cells with both wild and inactive type of p53. Furthermore, it was shown that wt-p53 was preferentially associated with Apo-MT. Our data suggest that co-expression of MT and p53 and their complex formation in tumor cells may be involved in regulation of apoptosis in these cells. [Copyright &y& Elsevier]