Downregulation of p21/WAF1 expression by thymidylate synthase

Evdokia K. Kastanos, Maria Zajac-Kaye, Phillip A. Dennis, Carmen J. Allegra

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


We developed a cell system where expression of thymidylate synthase (TS), an enzyme essential for DNA synthesis, can be modulated by a Zn2+-inducible promoter in MCF-7 cells. We found that overexpression of TS resulted in downregulation of p21 protein and mRNA levels. Statistical analysis demonstrated a significant downregulation of p21, but not a statistically significant decrease in p53 protein levels following TS induction. Since p21 is known to be transcriptionally activated by p53, these results suggest that TS downregulation of p21 may be occurring through a p53-independent mechanism in this in vitro cell system. In addition, cell cycle analysis demonstrated that downregulation of p21 by TS resulted in a decreased G1/S ratio in MCF-7 cells.

Original languageEnglish (US)
Pages (from-to)195-200
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Jan 1 2001


  • Thymidylate synthase induction
  • p21 downregulation
  • p53

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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