Vázquez-Macías Aleida, Ruíz-Mendoza Ana B, Fonseca-Sánchez Miguel A, Briones-Orta Marco A, Macías-Silva Marina
Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, DF 04510, Mexico.
FEBS Lett. 2005 Jul 4;579(17):3701-6. doi: 10.1016/j.febslet.2005.05.057.
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.
蛋白酶体途径调节转化生长因子-β（TGF-β）信号传导；活化的Smad2/3和受体的降解会关闭TGF-β信号，而Ski和SnoN等负调节因子的降解则维持该信号。我们发现茴香霉素能够像TGF-β一样通过蛋白酶体下调Ski和SnoN，但通过一种独立于Smad激活的机制。茴香霉素下调Ski和SnoN所使用的机制也独立于丝裂原活化蛋白激酶（MAPK）激活和蛋白质合成抑制。TGF-β信号是描述的导致Ski和SnoN降解的唯一途径，因此茴香霉素对内源性Ski和SnoN蛋白的这种新作用提示了下调TGF-β信号传导这些负调节因子的替代过程。
