The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo.
Journal:
Cell 2002 OctAuthors:
Fu L, Pelicano H, Liu J, Huang P, Lee C
Abstract
The Period2 gene plays a key role in controlling circadian rhythm in mice. We report here that mice deficient in the mPer2 gene are cancer prone. After gamma radiation, these mice show a marked increase in tumor development and reduced apoptosis in thymocytes. The core circadian genes are induced by gamma radiation in wild-type mice but not in mPer2 mutant mice. Temporal expression of genes involved in cell cycle regulation and tumor suppression, such as Cyclin D1, Cyclin A, Mdm-2, and Gadd45alp
...[more]ha, is deregulated in mPer2 mutant mice. In particular, the transcription of c-myc is controlled directly by circadian regulators and is deregulated in the mPer2 mutant. Our studies suggest that the mPer2 gene functions in tumor suppression by regulating DNA damage-responsive pathways.[less]
Mesh Headings:
ARNTL Transcription Factors, Animals, Apoptosis, Basic Helix-Loop-Helix Transcription Factors, Blotting, Northern, Blotting, Western, Cell Cycle, Cell Cycle Proteins, Cell Division, Cyclin A, Cyclin D1, DNA Damage, Dimerization, Flow Cytometry, Gamma Rays, Genetic Predisposition to Disease, Mice, Mice, Inbred C57BL, Mutation, Neoplasms, Experimental, Nerve Tissue Proteins, Nuclear Proteins, Period Circadian Proteins, Phenotype, Promoter Regions, Genetic, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Proto-Oncogene Proteins c-myc, Thymus Gland, Time Factors, Transcription Factors, Transfection, Tumor Suppressor Protein p53