Considering the relationship between abnormalities of UPS and carcinogenesis, we focus on FBXW7, a component of the SCF ubiquitin ligase complexes, which mainly serves as a tumor suppressor through ubiquitin-mediated degradation of its substrates, such as c-MYC, mTOR, MCL-1, Notch, c-Jun, and cyclin E. Being devoid of FBXW7 results in the accumulation of target proteins, demonstrated in in vitro and in vivo studies to impact the initiation, development, relapse, and therapeutic responses of multiple cancers. This evidence concerns the gene MCL1 and neoplasm.