Downregulation of SnoN oncoprotein induced by antibiotics anisomycin and puromycin positively regulates transforming growth factor-ß signals
Por:
Hernandez-Damian, J, Tecalco-Cruz, AC, Rios-Lopez, DG, Vazquez-Victorio, G, Vazquez-Macias, A, Caligaris, C, Sosa-Garrocho, M, Flores-Perez, B, Romero-Avila, M, Macias-Silva, M
Publicada:
1 nov 2013
Resumen:
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-ß (TGF-ß) 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-ß signaling was inhibited by using different pharmacological and non-pharmacological approaches, either by using specific TßRI inhibitors, overexpressing the inhibitory Smad7 protein, or knocking-down TßRI receptor or Smad2 by specific shRNAs. The outcome of SnoN and Ski downregulation induced by ANS or PURO on TGF-ß 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-ß 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-ß/Smad pathway to downregulate SnoN. In addition, SnoN protein downregulation induced by antibiotics favored gene transcription induced by TGF-ß signaling. Conclusions ANS and PURO require TGF-ß/Smad pathway to induce SnoN and Ski protein downregulation independently of inducing R-Smad2 phosphorylation, which facilitates TGF-ß signaling. General significance Antibiotic analogs lacking ribotoxic effects are useful as pharmacological tools to study TGF-ß signaling by controlling Ski and SnoN protein levels. © 2013 Elsevier B.V.
Filiaciones:
Hernandez-Damian, J:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol Celular & Desarrollo, Mexico City 04510, DF, Mexico
Tecalco-Cruz, AC:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol Celular & Desarrollo, Mexico City 04510, DF, Mexico
Rios-Lopez, DG:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol Celular & Desarrollo, Mexico City 04510, DF, Mexico
Vazquez-Victorio, G:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol Celular & Desarrollo, Mexico City 04510, DF, Mexico
Vazquez-Macias, A:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol Celular & Desarrollo, Mexico City 04510, DF, Mexico
Caligaris, C:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol Celular & Desarrollo, Mexico City 04510, DF, Mexico
Sosa-Garrocho, M:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol Celular & Desarrollo, Mexico City 04510, DF, Mexico
Flores-Perez, B:
Univ Nacl Autonoma Mexico, Fac Quim, Mexico City 04510, DF, Mexico
Romero-Avila, M:
Univ Nacl Autonoma Mexico, Fac Quim, Mexico City 04510, DF, Mexico
Macias-Silva, M:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol Celular & Desarrollo, Mexico City 04510, DF, Mexico
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