DNA alkylation-induced phosphorylation of p53 and activation of kinases in colon cancer cells

  • Authors:
    • Aruna S. Jaiswal
    • Satya Narayan
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  • Published online on: September 1, 2001     https://doi.org/10.3892/ijo.19.3.613
  • Pages: 613-616
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Abstract

In response to DNA damage, p53 protein transiently stabilizes and accumulates in the nucleus, where it performs its role as a transcription factor. Phosphorylation of p53 increases its sequence-specific DNA-binding activity. In the present study, we have examined the effect of methylmethane sulfonate (MMS) to HCT-116 human colon cancer cells on the phosphorylation of p53. Results show that p53 protein becomes phosphorylated at serine 15 (Ser15) and Ser392 residues after treatment with MMS in a time-dependent manner. Increased levels of phospho-p53(Ser15) and phospho-p53(Ser392) were maintained up to 50 h of the MMS treatment. We also examined the involvement of probable kinase(s), which could be responsible for MMS-induced phosphorylation of p53 at Ser15 and Ser392. In vitro phosphorylation assay, carried out with the immunoprecipates of MMS-treated cells, showed an increased phosphorylation of p53 by c-Jun kinase 1 (JNK1) at early time points (2.5 h). However, with cyclin-dependent kinase (Cdk2) and TFIIH complex associated kinase CAK, the phosphorylation of p53 was increased at later time points (25 h). The phosphorylation of p53 by Cdc2 and MAPK (p38) kinases remained unaffected in the MMS-treated versus untreated cells. The MMS-induced phosphorylation of p53 correlates with our previous findings of p53's ability for increased sequence-specific DNA-binding and transcriptional activity in the cells treated with DNA alkylating agents.

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September 2001
Volume 19 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Jaiswal AS and Jaiswal AS: DNA alkylation-induced phosphorylation of p53 and activation of kinases in colon cancer cells. Int J Oncol 19: 613-616, 2001
APA
Jaiswal, A.S., & Jaiswal, A.S. (2001). DNA alkylation-induced phosphorylation of p53 and activation of kinases in colon cancer cells. International Journal of Oncology, 19, 613-616. https://doi.org/10.3892/ijo.19.3.613
MLA
Jaiswal, A. S., Narayan, S."DNA alkylation-induced phosphorylation of p53 and activation of kinases in colon cancer cells". International Journal of Oncology 19.3 (2001): 613-616.
Chicago
Jaiswal, A. S., Narayan, S."DNA alkylation-induced phosphorylation of p53 and activation of kinases in colon cancer cells". International Journal of Oncology 19, no. 3 (2001): 613-616. https://doi.org/10.3892/ijo.19.3.613