Selenoprotein W depletion induces a p53- and p21-dependent delay in cell cycle progression in RWPE-1 prostate epithelial cells

Wayne Chris Hawkes, Ignat Printsev, Zeynep Alkan

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The anticancer activity of selenium (Se) has been demonstrated in myriad animal and in vitro studies, yet the mechanisms remain obscure. The main form of Se in animal tissues is selenocysteine in selenoproteins, but the relative importance of selenoproteins versus smaller Se compounds in cancer protection is unresolved. Selenoprotein W (SEPW1) is a highly conserved protein ubiquitously expressed in animals, bacteria, and archaea. SEPW1 depletion causes a delay in cell cycle progression at the G1/S transition of the cell cycle in breast and prostate epithelial cells. Tumor suppressor protein p53 is a master regulator of cell cycle progression and is the most frequently mutated gene in human cancers. p53 was increased in SEPW1 silenced cells and was inversely correlated with SEPW1 mRNA in cell lines with altered SEPW1 expression. Silencing SEPW1 decreased ubiquitination of p53 and increased p53 half-life. SEPW1 silencing increased p21(Cip1/WAF1/CDKN1A), while p27 (Kip1/CDKN1B) levels were unaffected. G1-phase arrest from SEPW1 knockdown was abolished by silencing p53 or p21. Cell cycle arrest from SEPW1 silencing was not associated with activation of ATM or phosphorylation of Ser-15 in p53, suggesting the DNA damage response pathway was not involved. Silencing GPX1 had no effect on cell cycle, suggesting that G1-phase arrest from SEPW1 silencing was not due to loss of antioxidant protection. More research is required to identify the function of SEPW1 and how it affects stability of p53.

Original languageEnglish (US)
Pages (from-to)61-69
Number of pages9
JournalJournal of Cellular Biochemistry
Volume113
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • Chemoprevention
  • G1/s transition
  • Selenium
  • Tumor suppressor protein
  • Ubiquitin

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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