Abstract
Despite increasing interest in human amniotic fluid cells, very little is known about the regulation and function of p53 in this cell type. In this study, we show that undifferentiated human amniotic fluid cells express p53, yet at lower levels than in cancer cells. The p53 protein in amniotic fluid cells is mainly localized in the nuclei, however, its antiproliferative activity is compromised in these cells. Igf2, a maternal imprinted gene, and c-jun, a proto-oncogene, are regulated by p53 in these cells. DNA damage leads to an increase in p53 abundance in human amniotic fluid cells and to transcriptional activation of its target genes. Interestingly, cell differentiation toward the neural lineage leads to p53 induction as differentiation progresses.
Highlights
IntroductionP53 was identified and ever since has remained at the core of cancer research
Almost four decades ago, p53 was identified and ever since has remained at the core of cancer research
Since human amniotic fluid stem (hAFS) cells are an intermediate between stem cells and more differentiated progenitor cells, [10] and since it has been shown that in murine embryonic stem (ES) cells, p53’s antiproliferative activity is compromised [14], we wondered whether p53 is able to suppress cell proliferation in hAFS cells
Summary
P53 was identified and ever since has remained at the core of cancer research. P53, which is encoded by the tp gene, is involved in a variety of cellular processes, including proliferation, senescence, differentiation, apoptosis, ferroptosis, DNA repair, metabolism, angiogenesis, and autophagy [4,5]. P53 is a transcription factor that elicits its cellular functions mostly through transcriptional activation of target genes. Apart from all the activities it plays in adult somatic cells, p53 seems to be involved in the self-renewal of embryonic stem (ES) cells and other adult stem cells, as well as in the onset of differentiation [7]. In adult stem cells like neural or hematopoietic stem cells, p53 negatively regulates proliferation and self-renewal, and helps to maintain their quiescent state [8,9]
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