| First Author | Lee JH | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 26 | Pages | 10668-72 |
| PubMed ID | 21628572 | Mgi Jnum | J:173314 |
| Mgi Id | MGI:5013855 | Doi | 10.1073/pnas.1106284108 |
| Citation | Lee JH, et al. (2011) From the Cover: Circadian clock disruption improves the efficacy of chemotherapy through p73-mediated apoptosis. Proc Natl Acad Sci U S A 108(26):10668-72 |
| abstractText | The circadian clock in mammalian organisms is generated by a transcription-translation feedback loop that controls many biochemical pathways at the cellular level and physiology and behavior at the organismal level. Cryptochrome (Cry) is a key protein in the negative arm of the transcription-translation feedback loop. It has been found that Cry mutation in cells with p53-null genotype increased their sensitivity to apoptosis by genotoxic agents. Here we show that this increased sensitivity is due to up-regulation of the p53 gene family member p73 in response to DNA damage. As a consequence, when tumors arising from oncogenic Ras-transformed p53(-/-) and p53(-/-)Cry1(-/-)Cry2(-/-) cells are treated with the anticancer drug oxaliplatin, p53(-/-) tumors continue to grow whereas p53(-/-)Cry1(-/-)Cry2(-/-) tumors exhibit extensive apoptosis and stop growing. This finding provides a mechanistic foundation for overcoming the resistance of p53-deficient tumor cells to apoptosis induced by DNA-damaging agents and suggests that disruption of cryptochrome function may increase the sensitivity of tumors with p53 mutation to chemotherapy. |
