Regulation of c-Maf and αA-Crystallin in Ocular Lens by Fibroblast Growth Factor Signaling.
J Biol Chem
; 291(8): 3947-58, 2016 Feb 19.
Article
en En
| MEDLINE
| ID: mdl-26719333
ABSTRACT
Fibroblast growth factor (FGF) signaling regulates a multitude of cellular processes, including cell proliferation, survival, migration, and differentiation. In the vertebrate lens, FGF signaling regulates fiber cell differentiation characterized by high expression of crystallin proteins. However, a direct link between FGF signaling and crystallin gene transcriptional machinery remains to be established. Previously, we have shown that the bZIP proto-oncogene c-Maf regulates expression of αA-crystallin (Cryaa) through binding to its promoter and distal enhancer, DCR1, both activated by FGF2 in cell culture. Herein, we identified and characterized a novel FGF2-responsive region in the c-Maf promoter (-272/-70, FRE). Both c-Maf and Cryaa regulatory regions contain arrays of AP-1 and Ets-binding sites. Chromatin immunoprecipitation (ChIP) assays established binding of c-Jun (an AP-1 factor) and Etv5/ERM (an Ets factor) to these regions in lens chromatin. Analysis of temporal and spatial expression of c-Jun, phospho-c-Jun, and Etv5/ERM in wild type and ERK1/2 deficient lenses supports their roles as nuclear effectors of FGF signaling in mouse embryonic lens. Collectively, these studies show that FGF signaling up-regulates expression of αA-crystallin both directly and indirectly via up-regulation of c-Maf. These molecular mechanisms are applicable for other crystallins and genes highly expressed in terminally differentiated lens fibers.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Factor 2 de Crecimiento de Fibroblastos
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Sistema de Señalización de MAP Quinasas
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Cristalinas
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Proteínas Proto-Oncogénicas c-maf
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Cristalino
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2016
Tipo del documento:
Article