The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo.
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 Gadd45alpha, 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.
Fu
Loning
L
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Pelicano
Helene
H
Liu
Jinsong
J
Huang
Peng
P
Lee
Cheng
C
D056930:ARNTL Transcription Factors; D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins; D015152:Blotting, Northern; D015153:Blotting, Western; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002455:Cell Division; D019925:Cyclin A / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D004249:DNA Damage; D019281:Dimerization; D005434:Flow Cytometry; D005720:Gamma Rays; D020022:Genetic Predisposition to Disease; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009374:Neoplasms, Experimental / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D056950:Period Circadian Proteins; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D000097642:GADD45 Proteins
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D019925:Cyclin A; D019938:Cyclin D1; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D011518:Proto-Oncogene Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C538960:BMAL1 protein, human; C538961:Bmal1 protein, mouse; C499072:Gadd45a protein, mouse; D000097642:GADD45 Proteins; C491259:Npas2 protein, mouse; C513312:Per2 protein, mouse; C497207:Mdm2 protein, mouse