Role of the p53 oncosuppressor gene family members in the expression regulation of the IGFBP3 gene

Insulin-like growth factors (IGFs), their common receptors (IGFIRs) and their binding proteins (IGFPBs) play a critical role in fetal and postnatal growth. Only exceptionally mutations or deletions of IGF-related genes have been reported in short children. For this reason, the attention has been focused on the functional study of IGF-related promoter genes in search of new regulatory elements and factors that might alter gene expression. Among these genes, IGFBP3 plays a key role because it transports more than 75% of serum IGFs, extends the half-life of IGFs and modulates their biological effects. In addition, IGFBP3 also has IGF-independent effects, including cell growth inhibition and induction of apoptosis. The literature reports that the IGFBP3 gene is a direct target of p53 and contains two p53 Responsive Elements (REs) located in intron 1 and intron 2: box A and box B, respectively. Moreover, it has been reported that ?Np63? down-regulates IGFBP3 expression.