P53 and IGFBP-3: apoptosis and cancer protection

Mol Genet Metab. 2000 Jun;70(2):85-98. doi: 10.1006/mgme.2000.3008.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis*
  • Genes, Tumor Suppressor
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / physiology*
  • Insulin-Like Growth Factor I / metabolism
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / prevention & control*
  • Tumor Suppressor Protein p53 / physiology*


  • Insulin-Like Growth Factor Binding Protein 3
  • Tumor Suppressor Protein p53
  • Insulin-Like Growth Factor I