Induction of p53-, MDM2-, and WAF1/CIP1-like molecules in insect cells by DNA-damaging agents.
Cellular responses following DNA damage are ubiquitous in the biological world. In response to DNA damage, cell cycle checkpoints are activated, which delay cell cycle progression and most likely serve to allow time for repair. One important checkpoint in mammalian cells, activated in the G1 phase of the cell cycle, is dependent on the p53 tumor suppressor gene product. While p53 is responsible for inducing G1 arrest, the product of the MDM2 gene is believed to alleviate the arrest, allowing continuation of the cell cycle after a transient delay. Inasmuch as MDM2 and WAF1/CIP1 are transactivated by p53, while MDM2 binds to and modulates the activity of p53, a "feedback loop" is thus created. This pathway has been highly conserved in mammalian cells, but its presence outside of vertebrates is unknown. By using human MDM2 and WAF1/CIP1 cDNA probes, and monoclonal antibodies to p53 and Mdm2, we demonstrate in insect cell lines evidence for the existence of p53-, MDM2-, and WAF1/CIP1-like molecules and a p53-regulated pathway following treatment by DNA-damaging agents.
Bae
I
I
Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Smith
M L
ML
Fornace
A J
AJ
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D004249:DNA Damage; D004330:Drosophila / Q000187:drug effects / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D008741:Methyl Methanesulfonate / Q000494:pharmacology*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2; D011839:Radiation, Ionizing; D018411:Spodoptera / Q000187:drug effects / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014466:Ultraviolet Rays
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D008741:Methyl Methanesulfonate; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2