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- Title
p53-Dependent and -Independent Epithelial Integrity: Beyond miRNAs and Metabolic Fluctuations.
- Authors
Oikawa, Tsukasa; Otsuka, Yutaro; Sabe, Hisataka
- Abstract
In addition to its classical roles as a tumor suppressor, p53 has also been shown to act as a guardian of epithelial integrity by inducing the microRNAs that target transcriptional factors driving epithelial–mesenchymal transition. On the other hand, the ENCODE project demonstrated an enrichment of putative motifs for the binding of p53 in epithelial-specific enhancers, such as <italic>CDH1</italic> (encoding E-cadherin) enhancers although its biological significance remained unknown. Recently, we identified two novel modes of epithelial integrity (i.e., maintenance of <italic>CDH1</italic> expression): one involves the binding of p53 to a <italic>CDH1</italic> enhancer region and the other does not. In the former, the binding of p53 is necessary to maintain permissive histone modifications around the <italic>CDH1</italic> transcription start site, whereas in the latter, p53 does not bind to this region nor affect histone modifications. Furthermore, these mechanisms likely coexisted within the same tissue. Thus, the mechanisms involved in epithelial integrity appear to be much more complex than previously thought. In this review, we describe our findings, which may instigate further experimental scrutiny towards understanding the whole picture of epithelial integrity as well as the related complex asymmetrical functions of p53. Such understanding will be important not only for cancer biology but also for the safety of regenerative medicine.
- Subjects
EPITHELIAL cells; TUMOR suppressor genes; CARCINOGENESIS; BINDING sites; GENE expression; HISTONES; METHYLATION; TRANSCRIPTION factors; CANCER cell culture; PHYSIOLOGY; CELL physiology
- Publication
Cancers, 2018, Vol 10, Issue 6, p162
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers10060162