title: A novel pathway of TEF regulation mediated by microRNA-125b contributes to the control of actin distribution and cell shape in fibroblasts.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unidad de Genetica Molecular, Hospital Universitario Marques de Valdecilla, Instituto de Formacion e Investigacion Marques de Valdecilla, Servicio Cantabro de Salud, Santander, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Gutierrez
authors.forename: Maria T
authors.initials: MT
authors.lastname: Berciano
authors.forename: Miguel
authors.initials: M
authors.lastname: Lafarga
authors.forename: Jose L
authors.initials: JL
authors.lastname: Fernandez-Luna
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency / Q000235:genetics*; D048430:Cell Shape / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000199:Actins; D050976:Basic-Leucine Zipper Transcription Factors; D035683:MicroRNAs; C527468:Mirn125 microRNA, mouse; C489491:Tef protein, mouse; D016159:Tumor Suppressor Protein p53