Genetic link between p53 and genes required for formation of the zonula adherens junction
Genetic link between p53 and genes required for formation of the zonula adherens junction
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DOI：
10.1111/j.1349-7006.2004.tb03228.x
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发表时间：
2004-05
期刊：
影响因子：
5.7
通讯作者：
M. Yamaguchi;F. Hirose;Y. Inoue;K. Ohno;H. Yoshida;Y. Hayashi;P. Deák;A. Matsukage
中科院分区：
文献类型：
--
作者：
M. Yamaguchi;F. Hirose;Y. Inoue;K. Ohno;H. Yoshida;Y. Hayashi;P. Deák;A. Matsukage
人p53基因在果蝇眼成虫盘细胞中的异位表达可诱导果蝇细胞凋亡并导致果蝇眼表型粗糙。我们已经筛选了果蝇种群，以确定增强或抑制p53诱导的粗糙眼表型的突变。p53诱导的粗糙眼表型的显性增强子之一对应于crumbs基因的功能缺失突变，这对于粘附小带连接的生物发生和上皮细胞中顶端极性的建立至关重要。通过TUNEL方法证实，通过将crumbs基因剂量减半，p53诱导的眼椎间盘细胞凋亡增强。此外，Shotgun（果蝇E‐cadherin）和Armadillo（果蝇β‐catenin）（粘附连接的两个主要成分）的基因突变也强烈增强了p53诱导的粗糙眼表型。这些结果表明，人p53在粘附连接处或在来自连接的信号中感觉到细微的异常，并因此诱导细胞凋亡以从组织中去除异常细胞。因此，p53可能不仅通过感知受损的DNA，而且还通过感知来自粘附连接的信号来发挥组织监护人的作用。
Ectopic expression of human p53 in Drosophila eye imaginal disc cells induces apoptosis and results in a rough eye phenotype in the adult flies. We have screened Drosophila stocks to identify mutations that enhance or suppress the p53‐induced rough eye phenotype. One of the dominant enhancers of the p53‐induced rough eye phenotype corresponds to a loss‐of‐function mutation of the crumbs gene, which is essential for the biogenesis of the zonula adherens junction and the establishment of apical polarity in epithelial cells. Enhancement of p53‐induced apoptosis in the eye imaginal discs by a half‐reduction of the crumbs gene dose was confirmed by a TUNEL method. Furthermore, mutations of genes for Shotgun (Drosophila E‐cadherin) and Armadillo (Drosophilaβ‐catenin), the two main components of the adherens junction, also strongly enhanced the p53‐induced rough eye phenotype. These results suggest that human p53 senses subtle abnormality at the adherens junction or in signals derived from the junction, and consequently induces apoptosis to remove abnormal cells from tissue. Thus p53 likely plays a role as a guardian of the tissue not only by sensing the damaged DNA, but also by sensing signals from the adherens junction.