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Induction of the growth inhibitor IGF-binding protein 3 by p53

Abstract

TRANSCRIPTIONAL activation of target genes represents an important component of the tumour-suppressor function of p53 and provides a functional link between p53 and various growth-regulatory processes, including cell cycle progression (p21/WAF1)1á¤-3, DNA repair (GADD45)4 and apoptosis (bax)5. Here we use a differential cloning approach to identify the gene encoding insulin-like growth factor binding protein 3 (IGF-BP3) as a novel p53-regulated target gene. Induction of IGF-BP3 gene expression by wild-type but not mutant p53 is associated with enhanced secretion of an active form of IGF-BP3 capable of inhibiting mitogenic signalling by the insulin-like growth factor IGF-1. Our results indicate that IGF-BP3 may link p53 to potential novel autocrine/paracrine signalling pathways and to processes regulated by or dependent on IGF(s), such as cellular growth, transformation and survival.

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Buckbinder, L., Talbott, R., Velasco-Miguel, S. et al. Induction of the growth inhibitor IGF-binding protein 3 by p53. Nature 377, 646–649 (1995). https://doi.org/10.1038/377646a0

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