p53-Dependent and -Independent Epithelial Integrity: Beyond miRNAs and Metabolic Fluctuations.
p53-Dependent and -Independent Epithelial Integrity: Beyond miRNAs and Metabolic Fluctuations.
复制标题
DOI：
10.3390/cancers10060162
复制
发表时间：
2018-05-25
期刊：
影响因子：
5.2
通讯作者：
Sabe H
中科院分区：
文献类型：
--
作者：
Oikawa T;Otsuka Y;Sabe H
除了作为肿瘤抑制因子的经典作用外，P53还被证明通过诱导针对转录因子的microRNAs来保护上皮的完整性，这些转录因子驱动上皮-间充质转化。另一方面，ENCODE项目表明，在上皮特异性增强子中，如CDH1(编码E-钙粘蛋白)增强子中，P53结合的假定基序丰富，尽管其生物学意义尚不清楚。最近，我们发现了两种新的上皮完整性模式(即维持CDH1的表达)：一种涉及P53与CDH1增强子区的结合，另一种则不涉及。在前者中，P53的结合是维持CDH1转录起始点周围允许的组蛋白修饰所必需的，而在后者中，P53不与该区域结合，也不影响组蛋白修饰。此外，这些机制很可能在同一组织内共存。因此，涉及上皮完整性的机制似乎比之前认为的要复杂得多。在这篇综述中，我们描述了我们的发现，这可能会引发进一步的实验检查，以了解上皮完整性的全貌以及相关的复杂的不对称功能的p53。这样的理解不仅对癌症生物学很重要，而且对再生医学的安全性也很重要。
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 CDH1 (encoding E-cadherin) enhancers although its biological significance remained unknown. Recently, we identified two novel modes of epithelial integrity (i.e., maintenance of CDH1 expression): one involves the binding of p53 to a CDH1 enhancer region and the other does not. In the former, the binding of p53 is necessary to maintain permissive histone modifications around the CDH1 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.
登录
查看更多内容
影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
29
作者：
Lee JV;Carrer A;Shah S;Snyder NW;Wei S;Venneti S;Worth AJ;Yuan ZF;Lim HW;Liu S;Jackson E;Aiello NM;Haas NB;Rebbeck TR;Judkins A;Won KJ;Chodosh LA;Garcia BA;Stanger BZ;Feldman MD;Blair IA;Wellen KE
通讯作者：
Wellen KE
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
64.5
作者：
Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
通讯作者：
Rinn JL
影响因子：
9.8
作者：
Jain AK;Allton K;Iacovino M;Mahen E;Milczarek RJ;Zwaka TP;Kyba M;Barton MC
通讯作者：
Barton MC