Murine pituitary tumor-transforming gene functions as a securin protein in insulin-secreting cells

J Endocrinol. 2006 Oct;191(1):45-53. doi: 10.1677/joe.1.06885.


Human pituitary tumor-transforming gene 1 (PTTG1) encodes a securin protein critically important in regulating chromosome separation. Murine PTTG (mPTTG) is 66% homologous to human PTTG1 and PTTG-null (PTTG-/-) mice exhibit pancreatic beta-cell hypoplasia and abnormal nuclear morphology with resultant diabetes. As we show that ductal beta-cell neogenesis is intact in PTTG-/- mice, we explored mechanism for defective beta-cell replication. We tested whether mPTTG exhibits securin properties in mouse insulin-secreting insulinoma MIN6 cells, using a live-cell system to monitor mitosis in cells transfected with an enhanced green fluorescent protein (EGFP)-tagged mPTTG conjugate (mPTTG-EGFP). To fulfill the criteria for securin properties, the protein should undergo degradation immediately before the metaphase-to-anaphase transition when expression levels are low, and should inhibit metaphase-to-anaphase transition when expression levels are high. EGFP itself did not undergo degradation throughout mitosis and high levels of EGFP per se did not affect normal mitosis progression (n=25). However, mPTTG-EGFP was degraded 2 min before the metaphase-to-anaphase transition when expression levels were low (n=19), and high mPTTG-EGFP levels blocked metaphase-to-anaphase transition in 13 cells. mPTTG-EGFP inhibited MIN6 cell proliferation and caused apoptosis. Immunocoprecipitation demonstrated binding of mPTTG-EGFP and separase. These results show that mPTTG exhibits properties consistent with a murine securin in insulin-secreting mouse cells and mPTTG overexpression inhibits cell proliferation, suggesting that defective beta-cell proliferation observed in PTTG-/- mice is likely due to abnormal cell-cycle progression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anaphase
  • Animals
  • Apoptosis
  • Blotting, Western / methods
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Endopeptidases / metabolism
  • Fluorescent Antibody Technique
  • Gene Expression
  • Green Fluorescent Proteins / genetics
  • Humans
  • Immunoprecipitation
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / metabolism*
  • Insulinoma
  • Metaphase
  • Mice
  • Mice, Knockout
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Securin
  • Separase
  • Transfection / methods


  • Cell Cycle Proteins
  • Neoplasm Proteins
  • Securin
  • enhanced green fluorescent protein
  • pituitary tumor-transforming protein 1, human
  • Green Fluorescent Proteins
  • Endopeptidases
  • ESPL1 protein, human
  • Separase