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.
Copyright 2000 Academic Press.