These results negated the possibility of Smad6-mediated transcriptional inhibition of PIAS3. As previous research showed that PIAS3 is post-transcriptionally repressed in glioma cell lines and regulated by proteasomal degradation8, we speculated that the ubiquitin-proteasome pathway is the underlying mechanism of nuclear-Smad6-mediated PIAS3 downregulation. This evidence concerns the gene SMAD6 and central nervous system cancer.