Insulin-like growth factor binding protein-3 (IGFBP-3) is a member of the IGFBP family. Human IGFBP-3 is comprised of 264 amino acids, of which the molecular mass is 28.7 kDa without any post-translational modifications. The primary structures of human IGFBP-3 consist of three distinct domains: a highly conserved cysteine-rich N- and C-terminal domains and a nonconserved central domain. Insulin-like growth factor binding protein-3 (IGFBP-3) is a p53 tumor suppressor-regulated protein and a major carrier for IGFs in circulation. Disruption of IGFBP-3 at transcriptional and post-translational levels has been implicated in the pathophysiology of many different types of cancer including breast, prostate, and lung cancer. The principal action of IGFBP-3 is to transport IGF-I and IGF-II in circulation, and, thereby, prolong the half-life of IGFs. IGFBP-3 can inhibit or enhance IGF actions, depending on cell types, the cellular environment, IGFBP-3 concentration, and post-translational modifications such as glycosylation, proteolysis, and phosphorylation. Moreover, IGFBP-3 inhibits insulin-stimulated glucose uptake into adipocytes independent of IGF.
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