DRP003875
MYC antagonizes anti-proliferative effect of TGF-beta by repressing TRIM26-mediated TAF7 degradation
The tumor suppressive function of transforming growth factor-beta (TGF-beta) is switched to tumor promoter in cancer cells. However, how this functional switch takes place remains rarely elucidated. Here we identified E3 ubiquitin ligase Trim26 as a novel TGF-beta target gene and found that TRIM26 ubiquitylates general transcription factor II D (TFIID) subunit TAF7 for degradation upon TGF-beta treatment. Genome-wide analysis revealed most of the ribosomal protein genes (RPGs) to be directly bound and regulated by TAF7 and TGF-beta downregulates RPGs expression in a TRIM26 dependent manner, leading to global translation decrease, proliferation arrest and apoptosis. Interestingly, sustained TGF-beta treatment induced the recovery of proliferation with concomitant amplification of Myc oncogenes. Overexpressed MYC binds to Trim26 gene promoter and represses TRIM26 induction by TGF-beta, thereby antagonizing cytostatic function of TGF-beta. Taken together, our findings revealed the novel functional interaction between TGF-beta signaling and MYC, by which MYC inhibits proliferation arrest by TGF-beta and promotes tumorigenesis.