Downregulation of Ski and SnoN co-repressors by anisomycin.
Proteasome pathway regulates TGF-beta signaling; degradation of activated Smad2/3 and receptors turns TGF-beta signal off, while degradation of negative modulators such as Ski and SnoN maintains the signal. We have found that anisomycin is able to downregulate Ski and SnoN via proteasome as TGF-beta does, but through a mechanism independent of Smad activation. The mechanism used by anisomycin to downregulate Ski and SnoN is also independent of MAPK activation and protein synthesis inhibition. TGF-beta signal was the only pathway described causing Ski and SnoN degradation, thus this new effect of anisomycin on endogenous Ski and SnoN proteins suggests alternative processes to downregulate these negative modulators of TGF-beta signaling.
Vázquez-Macías
Aleida
A
Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, DF 04510, Mexico.
Ruíz-Mendoza
Ana B
AB
Fonseca-Sánchez
Miguel A
MA
Briones-Orta
Marco A
MA
Macías-Silva
Marina
M
D000841:Anisomycin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D051906:Smad7 Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011500:Protein Synthesis Inhibitors; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C060615:SKIL protein, human; C497806:SMAD7 protein, human; D051906:Smad7 Protein; D015534:Trans-Activators; C060614:SKI protein, human; D000841:Anisomycin; D020929:Mitogen-Activated Protein Kinase Kinases; D046988:Proteasome Endopeptidase Complex