In normal cells, SMAD3 activity is inhibited by TRIM33, which ubiquitinates SMAD4, resulting in the disassembly of the SMADs transcriptional complex and a forced exit of SMAD2/3 from the nucleus.[35, 61] In cancer, forkhead box M1 interacts with SMAD3 to sustain activation of the SMAD3/SMAD4 complex in the nucleus through preventing TRIM33 from binding SMAD3 and ubiquitinating SMAD4.[62] Here, we show an additional mechanism by which TRIM24 activates SMAD3 transcriptional activity by its association with SMAD3 while disrupting TRIM33–SMAD3 interaction. The gene discussed is SMAD3; the disease is cancer.