P53 and IGFBP-3: apoptosis and cancer protection.
p53, perhaps the single most important human tumor suppressor, is commonly mutated in human cancers. Normally genotoxic stress and hypoxia activate p53, which, through DNA-specific transcription activation, transcriptional repression, and protein-protein interactions, triggers cell cycle arrest and apoptosis. One of the genes induced by p53 was identified as that encoding the insulin-like growth factor binding protein (IGFBP)-3. IGFBP-3 was originally defined by the somatomedin hypothesis as the principal carrier of IGF-I in the circulation and the primary regulator of the amount of free IGF-I available to interact with the IGF-1 receptor. However, there is accumulating evidence that IGFBP-3 can also cause apoptosis in an IGF-independent manner. Thus, IGFBP-3 induction by p53 constitutes a new means of cross-talk between the p53 and IGF axes, and suggests that the ultimate function of IGFBP-3 may be to serve a protective role against the potentially carcinogenic effects of growth hormone and IGF-I.
Grimberg
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Division of Pediatric Endocrinology, The University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
D000818:Animals; D017209:Apoptosis; D016147:Genes, Tumor Suppressor; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D018972:Insulin-Like Growth Factor Binding Protein 3; D016159:Tumor Suppressor Protein p53; D007334:Insulin-Like Growth Factor I