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

• Published in: Nature (London) Vol. 377; no. 6550; pp. 646 - 649
• Main Authors: Buckbinder, Leonard, Talbott, Randy, Velasco-Miguel, Susana, Takenaka, Ivone, Faha, Barbara, Seizinger, Bernd R, Kley, Nikolai
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 19-10-1995; Nature Publishing Group
• Subjects: Base Sequence; Binding Sites; Biological and medical sciences; Cell Division - physiology; Cell Line; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cloning; Cloning, Molecular; Deoxyribonucleic acid; DNA; DNA - metabolism; Doxorubicin - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Gene Expression Regulation - radiation effects; Genes; Growth Inhibitors - biosynthesis; Growth Inhibitors - genetics; Growth Inhibitors - secretion; Humans; Insulin-Like Growth Factor Binding Protein 3 - biosynthesis; Insulin-Like Growth Factor Binding Protein 3 - genetics; Insulin-Like Growth Factor Binding Protein 3 - secretion; Insulin-Like Growth Factor I - antagonists & inhibitors; Molecular and cellular biology; Molecular Sequence Data; Proteins; Signal Transduction; Tumor Cells, Cultured; Tumor Suppressor Protein p53 - physiology; Ultraviolet Rays; Human; Protein p53; Regulation(control); Insulin-like growth factor binding protein; Molecular interaction; Binding site; Gene expression; Tumor suppressor gene
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/377646a0

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), DNA repair (GADD45) and apoptosis (bax). 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.