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Regulation of c-Maf and αA-Crystallin in Ocular Lens by Fibroblast Growth Factor Signaling

Overview of attention for article published in Journal of Biological Chemistry, February 2016
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Title
Regulation of c-Maf and αA-Crystallin in Ocular Lens by Fibroblast Growth Factor Signaling
Published in
Journal of Biological Chemistry, February 2016
DOI 10.1074/jbc.m115.705103
Pubmed ID
Authors

Qing Xie, Rebecca McGreal, Raven Harris, Chun Y. Gao, Wei Liu, Lixing W. Reneker, Linda S. Musil, Ales Cvekl

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.

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Geographical breakdown

Country Count As %
United States 1 6%
Unknown 15 94%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 19%
Student > Bachelor 3 19%
Student > Master 3 19%
Student > Ph. D. Student 3 19%
Other 1 6%
Other 0 0%
Unknown 3 19%
Readers by discipline Count As %
Agricultural and Biological Sciences 6 38%
Biochemistry, Genetics and Molecular Biology 5 31%
Immunology and Microbiology 1 6%
Medicine and Dentistry 1 6%
Unknown 3 19%