The tumor suppressor p53 regulates Xist expression in certain cellular contexts.
Shahan Mamoor
Abstract
The tumor suppressor p53 has major functions in regulation of cell cycle that are common to nearly all cells (1-3) but also possesses tissue-specific functions that are less well understood (4). We discovered a relationship between p53 and the non-coding RNA X inactive specific transcripts, Xist (5), when comparing the whole transcription of human breast cancer cell lines based on p53 mutation status. Deletion of p53 in neural stem cells results in upregulation of Xist to a magnitude greater than a vast majority of the transcriptome, and Xist induction can also be observed upon deletion of p53 in mouse embryonic stem cells but not in mouse embryonic fibroblasts from day 13.5 or in cultured cells of the human breast epithelium, benign (MCF10A) and transformed (MCF7). Xist orchestrates X-inactivation; we show here that in certain cellular contexts the tumor suppressor p53 can influence expression of a non-coding RNA with sex-specific functions, suggesting solid tumors (which feature p53 mutation as a major genetic alteration) in females may possess unique biologic properties which involve or feature changes in Xist expression, like activation of p53 target genes (e.g., TIGAR) and transcriptional responses to genotoxic insults like ionizing radiation.