Camptothecin and Zeocin Can Increase p53 Levels during All Cell Cycle Stages

doi:10.1006/bbrc.2001.6073

Biochemical and Biophysical Research Communications

Volume 289, Issue 5, 21 December 2001, Pages 998-1009

https://doi.org/10.1006/bbrc.2001.6073 Get rights and content

Abstract

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.

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Regular ArticleCamptothecin and Zeocin Can Increase p53 Levels during All Cell Cycle Stages

Abstract

Cell

Cell

Cell

Cell

Methods Enzymol.

Biochim. Biophys. Acta

Biochem. Biophys. Acta

Cell

Participation of p53 protein in the cellular response to DNA damage

Cancer Res.

DNA strand breaks: The DNA template alterations that trigger p53-dependent DNA damage response pathways

Mol. Cell. Biol.

Induction of cellular p53 activity by DNA-damaging agents and growth arrest

Mol. Cell. Biol.

Regulation of p53 function and stability by phosphorylation

Mol. Cell. Biol.

Functional activation of p53 via phosphorylation following DNA damage by UV but not gamma radiation

Biochemistry

Ultraviolet radiation, but not gamma radiation or etoposide-induced DNA damage, results in the phosphorylation of the murine p53 protein at serine-389

Proc. Natl. Acad. Sci. USA

Increased and altered DNA binding of human p53 by S and G2/M but not G1 cyclin -dependent kinases

Nature

Definition of a consensus binding site for p53

Nat. Genet.

A transcriptionally active DNA-binding site for human p53 protein complexes

Mol. Cell. Biol.

p53 tagged sites from human genomic DNA

Hum. Mol. Genet.

The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases

Cell

14–3–3 sigma is a p53-regulated inhibitor of G2/M progression

Mol. Cell

ATM-dependent activation of p53 involves dephosphorylation and association with 14–3–3 proteins

Nat. Genet.

Gadd45 is a nuclear cell cycle regulated protein which interacts with p21Cip1

Oncogene

Regular Article
Camptothecin and Zeocin Can Increase p53 Levels during All Cell Cycle Stages