Cellular adhesion regulates p53 protein levels in primary human keratinocytes

To gain insight into p53 tissue-specific regulatory pathways and biological activities, we investigated mechanisms that may account for the elevated levels of p53 protein in human foreskin keratinocytes, relative to levels in dermal fibroblasts in vitro. Here, we report that the loss of cell anchorage resulted in an approximately 5-fold decrease in p53 levels in keratinocytes, which was reversible upon reattachment of cells to a substratum. In contrast, fibroblasts did not exhibit such adhesion-dependent regulation of p53 protein. Furthermore, p53 function was attenuated in keratinocytes relative to fibroblasts. These results link p53 to cell adhesion pathways and may provide a molecular basis for epigenetic differences in the maintenance of genomic stability among normal cell types.