Genetic link between p53 and genes required for formation of the zonula adherens junction.
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 (Drosophila beta-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.
Yamaguchi
Masamitsu
M
Department of Applied Biology, Faculty of Textile Science, Drosophila Genetic Resource Center, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585, Japan. myamaguc@ipc.kit.ac.jp
Hirose
Fumiko
F
Inoue
Yoshihiro H
YH
Ohno
Katsuhito
K
Yoshida
Hideki
H
Hayashi
Yuko
Y
Deak
Peter
P
Matsukage
Akio
A
D022005:Adherens Junctions / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D004249:DNA Damage; D004330:Drosophila / Q000235:genetics*; D005123:Eye / Q000196:embryology; D016158:Genes, p53; D006801:Humans; D020287:In Situ Nick-End Labeling; D009154:Mutation; D010641:Phenotype; D015398:Signal Transduction