IGF-1 induces Pin1 expression in promoting cell cycle S-phase entry

Han You, Hongwu Zheng, Steven A. Murray, Qiang Yu, Takafumi Uchida, Daiming Fan, Zhi Xiong Jim Xiao

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)


Insulin-like growth factor I (IGF-1) is a well-established mitogen to many different cell types and is implicated in progression of a number of human cancers, notably breast cancer. The prolyl isomerase Pin1 plays an important role in cell cycle regulation through its specific interaction with proteins that are phosphorylated at Ser/Thr-Pro motifs. Pin1 knockout mice appear to have relatively normal development yet the Pin1-/- mouse embryo fibroblast (MEF) cells are defective in re-entering cell cycle in response to serum stimulation after G0 arrest. Here, we report that Pin1-/- MEF cells display a delayed cell cycle S-phase entry in response to IGF stimulation and that IGF-1 induces Pin1 protein expression which correlates with the induction of cyclin D1 and RB phosphorylation in human breast cancer cells. The induction of Pin1 by IGF-1 is mediated via the phosphatidylinositol 3-kinase as well as the MAP kinase pathways. Treatment of PI3K inhibitor LY294002 and the MAP kinase inhibitor PD098059, but not p38 inhibitor SB203580, effectively blocks IGF-1-induced upregulation of Pin1, cyclin D1 and RB phosphorylation. Furthermore, we found that Cyclin D1 expression and RB phosphorylation are dramatically decreased in Pin1-/- MEF cells. Reintroducing a recombinant adenovirus encoding Pin1 into Pin1-/- MEF cells restores the expression of cyclin D1 and RB phosphorylation. Thus, these data suggest that the mitogenic function of IGF-1 is at least partially linked to the induction of Pin1, which in turn stimulates cyclin D1 expression and RB phosphorylation, therefore contributing to G0/G1-S transition.

Original languageEnglish
Pages (from-to)211-216
Number of pages6
JournalJournal of Cellular Biochemistry
Issue number2
Publication statusPublished - 2002
Externally publishedYes


  • Cell cycle
  • Cyclin D
  • IGF-1
  • Pin-1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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