Camptothecin and Zeocin can increase p53 levels during all cell cycle stages.
The ability of DNA damage to stabilize p53 in all cell cycle stages has not been examined in actively growing cells. The chemotherapeutic drug camptothecin is a topoisomerase I poison. Zeocin is a member of the bleomycin/phleomycin family of antibiotics, known to bind DNA. Both increase the level of p53 albeit by different mechanisms. We have utilized centrifugal elutriation to separate exponentially growing ML-1 cells (containing wild-type p53) into cell cycle fractions and have subsequently treated these cells with the two drugs. We provide evidence that both drugs can mediate an increase in p53 protein levels independent of the cell cycle stage. The p53 induced by both drugs was able to bind to DNA; however, only the p53 induced by camptothecin was phosphorylated at serine-392. This is the first demonstration that camptothecin and Zeocin can differentially signal for increased levels of modified p53 during all stages of the cell cycle.
Houser
S
S
Institute for Biomolecular Structure and Function, Department of Biological Sciences, Hunter College and Graduate School, City University of New York, 695 Park Avenue, New York 10021, USA.
Koshlatyi
S
S
Lu
T
T
Gopen
T
T
Bargonetti
J
J
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology*; D002166:Camptothecin / Q000494:pharmacology*; D002453:Cell Cycle / Q000502:physiology*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000378:metabolism; D004355:Drug Stability; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D012694:Serine / Q000737:chemistry; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D001761:Bleomycin; C105427:Zeocin; D012694:Serine; D002166:Camptothecin