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The p53 family member p73 modulates the proproliferative role of IGFBP3 in short children born small for gestational age

The regulation of insulin-like growth factor–binding protein 3 (IGFBP3) gene expression is complex, because it can be induced by agents that both stimulate and inhibit the proliferation. The principal aim of this study was to investigate whether p73, a member of the p53 gene family, has a role in th...

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Autores principales: Marzano, Flaviana, Ventura, Annamaria, Francesco Caratozzolo, Mariano, Aiello, Italia, Mastropasqua, Francesca, Brunetti, Giacomina, Cavallo, Luciano, Sbisà, Elisabetta, Faienza, Maria Felicia, Tullo, Apollonia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571334/
https://www.ncbi.nlm.nih.gov/pubmed/26063735
http://dx.doi.org/10.1091/mbc.E15-02-0105
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author Marzano, Flaviana
Ventura, Annamaria
Francesco Caratozzolo, Mariano
Aiello, Italia
Mastropasqua, Francesca
Brunetti, Giacomina
Cavallo, Luciano
Sbisà, Elisabetta
Faienza, Maria Felicia
Tullo, Apollonia
author_facet Marzano, Flaviana
Ventura, Annamaria
Francesco Caratozzolo, Mariano
Aiello, Italia
Mastropasqua, Francesca
Brunetti, Giacomina
Cavallo, Luciano
Sbisà, Elisabetta
Faienza, Maria Felicia
Tullo, Apollonia
author_sort Marzano, Flaviana
collection PubMed
description The regulation of insulin-like growth factor–binding protein 3 (IGFBP3) gene expression is complex, because it can be induced by agents that both stimulate and inhibit the proliferation. The principal aim of this study was to investigate whether p73, a member of the p53 gene family, has a role in the regulation of the IGFBP3 expression and whether this regulation occurs in a context of cell survival or death. We demonstrate that IGFBP3 is a direct TAp73α (the p73 isoform that contains the trans-activation domain) target gene and activates the expression of IGFBP3 in actively proliferating cells. As IGFBP3 plays a key role in regulating the growth hormone/insulin-like growth factor type 1 (GH/IGF1) axis, whose alterations in gene expression appear to have a role in the growth failure of children born small for gestational age (SGA), we measured the mRNA expression levels of p73 and IGFBP3 in a group of SGA children. We found that mRNA expression levels of p73 and IGFBP3 are significantly lower in SGA children compared with controls and, in particular, p73 mRNA expression is significantly lower in SGA children with respect to height. Our results shed light on the intricate GH/IGF pathway, suggesting p73 as a good biomarker of the clinical risk for SGA children to remain short in adulthood.
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spelling pubmed-45713342015-10-16 The p53 family member p73 modulates the proproliferative role of IGFBP3 in short children born small for gestational age Marzano, Flaviana Ventura, Annamaria Francesco Caratozzolo, Mariano Aiello, Italia Mastropasqua, Francesca Brunetti, Giacomina Cavallo, Luciano Sbisà, Elisabetta Faienza, Maria Felicia Tullo, Apollonia Mol Biol Cell Articles The regulation of insulin-like growth factor–binding protein 3 (IGFBP3) gene expression is complex, because it can be induced by agents that both stimulate and inhibit the proliferation. The principal aim of this study was to investigate whether p73, a member of the p53 gene family, has a role in the regulation of the IGFBP3 expression and whether this regulation occurs in a context of cell survival or death. We demonstrate that IGFBP3 is a direct TAp73α (the p73 isoform that contains the trans-activation domain) target gene and activates the expression of IGFBP3 in actively proliferating cells. As IGFBP3 plays a key role in regulating the growth hormone/insulin-like growth factor type 1 (GH/IGF1) axis, whose alterations in gene expression appear to have a role in the growth failure of children born small for gestational age (SGA), we measured the mRNA expression levels of p73 and IGFBP3 in a group of SGA children. We found that mRNA expression levels of p73 and IGFBP3 are significantly lower in SGA children compared with controls and, in particular, p73 mRNA expression is significantly lower in SGA children with respect to height. Our results shed light on the intricate GH/IGF pathway, suggesting p73 as a good biomarker of the clinical risk for SGA children to remain short in adulthood. The American Society for Cell Biology 2015-08-01 /pmc/articles/PMC4571334/ /pubmed/26063735 http://dx.doi.org/10.1091/mbc.E15-02-0105 Text en © 2015 Marzano et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Marzano, Flaviana
Ventura, Annamaria
Francesco Caratozzolo, Mariano
Aiello, Italia
Mastropasqua, Francesca
Brunetti, Giacomina
Cavallo, Luciano
Sbisà, Elisabetta
Faienza, Maria Felicia
Tullo, Apollonia
The p53 family member p73 modulates the proproliferative role of IGFBP3 in short children born small for gestational age
title The p53 family member p73 modulates the proproliferative role of IGFBP3 in short children born small for gestational age
title_full The p53 family member p73 modulates the proproliferative role of IGFBP3 in short children born small for gestational age
title_fullStr The p53 family member p73 modulates the proproliferative role of IGFBP3 in short children born small for gestational age
title_full_unstemmed The p53 family member p73 modulates the proproliferative role of IGFBP3 in short children born small for gestational age
title_short The p53 family member p73 modulates the proproliferative role of IGFBP3 in short children born small for gestational age
title_sort p53 family member p73 modulates the proproliferative role of igfbp3 in short children born small for gestational age
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571334/
https://www.ncbi.nlm.nih.gov/pubmed/26063735
http://dx.doi.org/10.1091/mbc.E15-02-0105
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