title: Downregulation of SnoN oncoprotein induced by antibiotics anisomycin and puromycin positively regulates transforming growth factor-β signals.
abstract: BACKGROUND
  SnoN and Ski proteins function as Smad transcriptional corepressors and are implicated in the regulation of diverse cellular processes such as proliferation, differentiation and transformation. Transforming growth factor-β (TGF-β) signaling causes SnoN and Ski protein degradation via proteasome with the participation of phosphorylated R-Smad proteins. Intriguingly, the antibiotics anisomycin (ANS) and puromycin (PURO) are also able to downregulate Ski and SnoN proteins via proteasome.
  
  
  METHODS
  We explored the effects of ANS and PURO on SnoN protein downregulation when the activity of TGF-β signaling was inhibited by using different pharmacological and non-pharmacological approaches, either by using specific TβRI inhibitors, overexpressing the inhibitory Smad7 protein, or knocking-down TβRI receptor or Smad2 by specific shRNAs. The outcome of SnoN and Ski downregulation induced by ANS or PURO on TGF-β signaling was also studied.
  
  
  RESULTS
  SnoN protein downregulation induced by ANS and PURO did not involve the induction of R-Smad phosphorylation but it was abrogated after TGF-β signaling inhibition; this effect occurred in a cell type-specific manner and independently of protein synthesis inhibition or any other ribotoxic effect. Intriguingly, antibiotics seem to require components of the TGF-β/Smad pathway to downregulate SnoN. In addition, SnoN protein downregulation induced by antibiotics favored gene transcription induced by TGF-β signaling.
  
  
  CONCLUSIONS
  ANS and PURO require TGF-β/Smad pathway to induce SnoN and Ski protein downregulation independently of inducing R-Smad2 phosphorylation, which facilitates TGF-β signaling.
  
  
  CONCLUSIONS
  Antibiotic analogs lacking ribotoxic effects are useful as pharmacological tools to study TGF-β signaling by controlling Ski and SnoN protein levels.
authors.affiliation: Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F., 04510 Mexico.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Hernández-Damián
authors.forename: Angeles C
authors.initials: AC
authors.lastname: Tecalco-Cruz
authors.forename: Diana G
authors.initials: DG
authors.lastname: Ríos-López
authors.forename: Genaro
authors.initials: G
authors.lastname: Vázquez-Victorio
authors.forename: Aleida
authors.initials: A
authors.lastname: Vázquez-Macías
authors.forename: Cassandre
authors.initials: C
authors.lastname: Caligaris
authors.forename: Marcela
authors.initials: M
authors.lastname: Sosa-Garrocho
authors.forename: Blas
authors.initials: B
authors.lastname: Flores-Pérez
authors.forename: Margarita
authors.initials: M
authors.lastname: Romero-Avila
authors.forename: Marina
authors.initials: M
authors.lastname: Macías-Silva
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008907:Mink / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011691:Puromycin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D015513:Oncogene Proteins; D051899:Smad2 Protein; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1; D011691:Puromycin; D000841:Anisomycin
keywords: Anisomycin; Puromycin; Ski corepressor; Smad transcriptional factor; SnoN corepressor; TGF-β cytokine