A novel pathway of TEF regulation mediated by microRNA-125b contributes to the control of actin distribution and cell shape in fibroblasts

• Published in: PloS one Vol. 6; no. 2; p. e17169
• Main Authors: Gutierrez, Olga, Berciano, Maria T, Lafarga, Miguel, Fernandez-Luna, Jose L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11-02-2011; Public Library of Science (PLoS)
• Subjects: Actin; Actins - metabolism; Amino acids; Animals; Apoptosis; Basic-Leucine Zipper Transcription Factors - deficiency; Basic-Leucine Zipper Transcription Factors - genetics; Biology; Bipolarity; Cancer; Cell cycle; Cell Shape - genetics; Cell size; Comparative analysis; Control; Cytoskeleton; Down-Regulation - genetics; Elongation; Embryo fibroblasts; Embryos; Enzymes; Fibroblasts; Fibroblasts - cytology; Fibroblasts - metabolism; Gene expression; Gene Silencing; Genotoxicity; HEK293 Cells; Homeostasis; Humans; Leukemia; Metabolism; Mice; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Muscle proteins; p53 Protein; Physiological aspects; Proteins; Regulations; Ribonucleic acid; RNA; Smooth muscle; Thyrotroph embryonic factor; Transcription; Transcription factors; Transfection; Trends; Tumor proteins; Tumor Suppressor Protein p53 - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0017169

Thyrotroph embryonic factor (TEF), a member of the PAR bZIP family of transcriptional regulators, has been involved in neurotransmitter homeostasis, amino acid metabolism, and regulation of apoptotic proteins. In spite of its relevance, nothing is known about the regulation of TEF.
p53-dependent genotoxic agents have been shown to be much more harmful for PAR bZIP-deficient mice as compared to wild type animals. Here we demonstrate that TEF expression is controlled by p53 through upregulation of microRNA-125b, as determined by both regulating the activity of p53 and transfecting cells with microRNA-125b precursors. We also describe a novel role for TEF in controlling actin distribution and cell shape in mouse fibroblasts. Lack of TEF is accompanied by dramatic increase of cell area and decrease of elongation (bipolarity) and dispersion (multipolarity). Staining of actin cytoskeleton also showed that TEF (-/-) cells are characterized by appearance of circumferential actin bundles and disappearance of straight fibers. Interestingly, transfection of TEF (-/-) fibroblasts with TEF induced a wild type-like phenotype. Consistent with our previous findings, transfection of wild type fibroblasts with miR-125b promoted a TEF (-/-)-like phenotype, and a similar but weaker effect was observed following exogenous expression of p53.
These findings provide the first evidence of TEF regulation, through a miR-125b-mediated pathway, and describes a novel role of TEF in the maintenance of cell shape in fibroblasts.