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

You, H., Zheng, H. W., Murray, S. A., Yu, Q., Uchida, T., Fan, D. M., Xiao, Z. X. J. (2002) IGF-1 induces Pin1 expression in promoting cell cycle S-phase entry. Journal of Cellular Biochemistry, 84 (2). pp. 211-216. ISSN 0730-2312

URL: http://www.ncbi.nlm.nih.gov/pubmed/11787050
DOI: 10.1002/jcb.10037

Abstract

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 Pin(-/-) mouse embryo fibroblast (MEF) cells are defective in re-entering cell cycle in response to serum stimulation after GO 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 DI 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 DI 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. (C) 2001 Wiley-Liss, Inc.

Item Type: Paper
Uncontrolled Keywords: IGF-1 Pin-1 cyclin D cell cycle HUMAN-BREAST-CANCER PHOSPHATIDYLINOSITOL 3-KINASE PROLYL ISOMERIZATION REGULATORY MECHANISM GROWTH-FACTORS MCF-7 PHOSPHORYLATION INSULIN PATHWAY MITOSIS Biochemistry & Molecular Biology Cell Biology
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > Cyclins
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > IGF
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > Pin 1
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle
CSHL Authors:
Communities: CSHL labs > Zheng lab
Depositing User: Matt Covey
Date: 2002
Date Deposited: 22 Aug 2014 16:30
Last Modified: 22 Aug 2014 16:30
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30714

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