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), 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.

Keywords

Autocrine signallingParacrine signallingGrowth factorCell biologyBiologyGadd45Insulin-like growth factorGeneCell growthRegulation of gene expressionCell cycleCell cycle checkpointReceptorGenetics

MeSH Terms

Base SequenceBinding SitesCell DivisionCell LineCloningMolecularDNADoxorubicinGene Expression RegulationGrowth InhibitorsHumansInsulin-Like Growth Factor Binding Protein 3Insulin-Like Growth Factor IMolecular Sequence DataSignal TransductionTumor CellsCulturedTumor Suppressor Protein p53Ultraviolet Rays

Affiliated Institutions

Bristol-Myers Squibb (Germany) DE

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Publication Info

Year: 1995
Type: article
Volume: 377
Issue: 6550
Pages: 646-649
Citations: 877
Access: Closed

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APA Style

                            
                                
                                    Leonard Buckbinder, 
                                
                                    Randy Talbott, 
                                
                                    Susana Velasco-Miguel
                                
                                et al.
                            
                            (1995). 
                            Induction of the growth inhibitor IGF-binding protein 3 by p53. 
                            Nature
                            , 377
                            (6550)
                            , 646-649.
                            https://doi.org/10.1038/377646a0
                        

Identifiers

DOI: 10.1038/377646a0
PMID: 7566179

Data Quality

Data completeness: 81%