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CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis

The expression of the forkhead transcription factor checkpoint suppressor 1 (CHES1), also known as FOXN3, is reduced in many types of cancers. We show here that CHES1 decreases protein synthesis and cell proliferation in tumor cell lines but not in normal fibroblasts. Conversely, short hairpin RNA–m...

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Autores principales: Huot, Geneviève, Vernier, Mathieu, Bourdeau, Véronique, Doucet, Laurent, Saint-Germain, Emmanuelle, Gaumont-Leclerc, Marie-France, Moro, Alejandro, Ferbeyre, Gerardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937083/
https://www.ncbi.nlm.nih.gov/pubmed/24403608
http://dx.doi.org/10.1091/mbc.E13-02-0110
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author Huot, Geneviève
Vernier, Mathieu
Bourdeau, Véronique
Doucet, Laurent
Saint-Germain, Emmanuelle
Gaumont-Leclerc, Marie-France
Moro, Alejandro
Ferbeyre, Gerardo
author_facet Huot, Geneviève
Vernier, Mathieu
Bourdeau, Véronique
Doucet, Laurent
Saint-Germain, Emmanuelle
Gaumont-Leclerc, Marie-France
Moro, Alejandro
Ferbeyre, Gerardo
author_sort Huot, Geneviève
collection PubMed
description The expression of the forkhead transcription factor checkpoint suppressor 1 (CHES1), also known as FOXN3, is reduced in many types of cancers. We show here that CHES1 decreases protein synthesis and cell proliferation in tumor cell lines but not in normal fibroblasts. Conversely, short hairpin RNA–mediated depletion of CHES1 increases tumor cell proliferation. Growth suppression depends on the CHES1 forkhead DNA-binding domain and correlates with the nuclear localization of CHES1. CHES1 represses the expression of multiple genes, including the kinases PIM2 and DYRK3, which regulate protein biosynthesis, and a number of genes in cilium biogenesis. CHES1 binds directly to the promoter of PIM2, and in cells expressing CHES1 the levels of PIM2 are reduced, as well as the phosphorylation of the PIM2 target 4EBP1. Overexpression of PIM2 or eIF4E partially reverses the antiproliferative effect of CHES1, indicating that PIM2 and protein biosynthesis are important targets of the antiproliferative effect of CHES1. In several human hematopoietic cancers, CHES1 and PIM2 expressions are inversely correlated, suggesting that repression of PIM2 by CHES1 is clinically relevant.
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spelling pubmed-39370832014-05-16 CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis Huot, Geneviève Vernier, Mathieu Bourdeau, Véronique Doucet, Laurent Saint-Germain, Emmanuelle Gaumont-Leclerc, Marie-France Moro, Alejandro Ferbeyre, Gerardo Mol Biol Cell Articles The expression of the forkhead transcription factor checkpoint suppressor 1 (CHES1), also known as FOXN3, is reduced in many types of cancers. We show here that CHES1 decreases protein synthesis and cell proliferation in tumor cell lines but not in normal fibroblasts. Conversely, short hairpin RNA–mediated depletion of CHES1 increases tumor cell proliferation. Growth suppression depends on the CHES1 forkhead DNA-binding domain and correlates with the nuclear localization of CHES1. CHES1 represses the expression of multiple genes, including the kinases PIM2 and DYRK3, which regulate protein biosynthesis, and a number of genes in cilium biogenesis. CHES1 binds directly to the promoter of PIM2, and in cells expressing CHES1 the levels of PIM2 are reduced, as well as the phosphorylation of the PIM2 target 4EBP1. Overexpression of PIM2 or eIF4E partially reverses the antiproliferative effect of CHES1, indicating that PIM2 and protein biosynthesis are important targets of the antiproliferative effect of CHES1. In several human hematopoietic cancers, CHES1 and PIM2 expressions are inversely correlated, suggesting that repression of PIM2 by CHES1 is clinically relevant. The American Society for Cell Biology 2014-03-01 /pmc/articles/PMC3937083/ /pubmed/24403608 http://dx.doi.org/10.1091/mbc.E13-02-0110 Text en © 2014 Huot 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 of Cell Biology.
spellingShingle Articles
Huot, Geneviève
Vernier, Mathieu
Bourdeau, Véronique
Doucet, Laurent
Saint-Germain, Emmanuelle
Gaumont-Leclerc, Marie-France
Moro, Alejandro
Ferbeyre, Gerardo
CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis
title CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis
title_full CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis
title_fullStr CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis
title_full_unstemmed CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis
title_short CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis
title_sort ches1/foxn3 regulates cell proliferation by repressing pim2 and protein biosynthesis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937083/
https://www.ncbi.nlm.nih.gov/pubmed/24403608
http://dx.doi.org/10.1091/mbc.E13-02-0110
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