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Review
. 2009 Aug;30(5):417-37.
doi: 10.1210/er.2008-0028. Epub 2009 May 28.

Unraveling insulin-like growth factor binding protein-3 actions in human disease

Sherryline Jogie-Brahim  1 , David Feldman, Youngman Oh
Affiliations
Review

Unraveling insulin-like growth factor binding protein-3 actions in human disease

Sherryline Jogie-Brahim et al. Endocr Rev. 2009 Aug.

Abstract

The IGF system plays critical roles in somatic growth in an endocrine fashion (somatomedin hypothesis) as well as proliferation and differentiation of normal and malignant cells in a paracrine/autocrine fashion. IGFBP-3 is known to modulate the actions of IGFs in circulation as well as the immediate extracellular environment. Interestingly, apart from the ability to inhibit or enhance IGF actions, IGFBP-3 also exhibits very clear, distinct biological effects independent of the IGF/IGF-I receptor axis. Over the past decade it has become widely appreciated that IGF/IGF-IR-independent actions of IGFBP-3 (antiproliferative and proapoptotic effects) contribute to improving the pathophysiology of a variety of human diseases, such as cancer, diabetes, and malnutrition. Recent studies have implicated interaction of IGFBP-3 with a variety of proteins or signaling cascades critical to cell cycle control and apoptosis; however, the actual mechanism of IGFBP-3 action is still unclear. This review reinforces the concept in support of the IGF/IGF-IR axis-independent actions of IGFBP-3 and delineates potential underlying mechanisms involved and subsequent biological significance, focusing in particular on functional binding partners and the clinical significance of IGFBP-3 in the assessment of cancer risk.

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Figures

Figure 1
Figure 1
Structure of human IGFBP-3. This figure depicts the three distinct domains of the IGFBP-3 molecule and lists the important functions and motifs of each of these key regions. The vertical lines represent cysteine residues.
Figure 2
Figure 2
IGF/IGF-IR-dependent and IGF/IGF-IR-independent actions of IGFBP-3.
Figure 3
Figure 3
Nuclear localization of IGFBP-3. In response to IGFBP-3, Nur77 rapidly translocates from the nucleus to the mitochondria and induces apoptosis.
See this image and copyright information in PMC

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