Human lactoferrin controls the level of retinoblastoma protein and its activity

Hee Joung Son, Shin Hee Lee, Sang Yun Choi

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Lactoferrin (Lf) has been implicated in the regulation of cell growth. However, the molecular mechanism underlying this effect remains to be elucidated. In this study, we show that Lf is involved in the cell cycle control system in a variety of cell lines, through retinoblastoma protein (Rb) - mediated growth arrest. We observed that Lf induces the expression of Rb, a signal mediator of cell cycle control, and that a majority of this Lf-induced Rb persists in a hypophosphorylated form. In addition, we determined that Lf specifically augments the level of a cyclin-dependent kinase inhibitor, p21, but not p27. Upon treatment with Lf, H1299 cells expressing defective p53 effected an augmentation of endogenous p21 levels, which may contribute to the accumulation of hypophosphorylated Rb. A substantial quantity of active Rb binds more efficiently to E2F1 in cells that express Lf and consequently blocks the expression of an E2F1-responsive gene, thereby suggesting that Lf plays a crucial role in the inhibition of tumor cell growth. Therefore, we conclude that the antiproliferative effects of Lf can likely be attributed to the elevated levels of hypophosphorylated Rb.

Original languageEnglish
Pages (from-to)345-350
Number of pages6
JournalBiochemistry and Cell Biology
Volume84
Issue number3
DOIs
Publication statusPublished - 2006 Jun

Keywords

  • Cyclin-dependent kinase inhibitor
  • E2F1
  • Lactoferrin
  • Retinoblastoma protein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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