Impaired regulation of tumor suppressor p53 caused by mutations in the xeroderma pigmentosum DDB2 gene: mutual regulatory interactions between p48(DDB2) and p53 |
| |
Authors: | Itoh Toshiki O'Shea Cristin Linn Stuart |
| |
Institution: | Division of Biochemistry and Molecular Biology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3202, USA. |
| |
Abstract: | Tumor suppressor p53 controls cell cycle progression and apoptosis following DNA damage, thus minimizing carcinogenesis. Mutations in the human DDB2 gene generate the E subgroup of xeroderma pigmentosum (XP-E). We report here that XP-E strains are defective in UV irradiation-induced apoptosis due to severely reduced basal and UV-induced p53 levels. These defects are restored by infection with a p53 cDNA expression construct or with a DDB2 expression construct if and only if it contains intron 4, which includes a nonmutated p53 consensus-binding site. We propose that both before and after UV irradiation, DDB2 directly regulates p53 levels, while DDB2 expression is itself regulated by p53. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|