Smad3 poly-ubiquitylation and proteasomal degradation can also be enhanced by the presence of the tumor suppressor protein ductal epithelium–associated ring chromosome 1 (DEAR1)/tripartite motif-containing 62 (TRIM62); tumor cells that carry loss of function mutations in DEAR1/TRIM62 exhibit enhanced Smad3 and corresponding TGFβ signaling levels, promoting the expression of Snail1 and Snail2 and downstream EMT [100]. The gene discussed is TGFB1; the disease is neoplasm.