Figure 1

Role of Fbxo45 in regulating apoptosis by promoting the degradation of Par-4 in cancer cells. In carcinoma cells, Par-4 triggers cellular apoptosis through activation of caspase 9. Moreover, Par-4 suppresses tumorigenesis via translocating to the nucleus, an event that is promoted by PKA-dependent phosphorylation, and subsequently inhibits NF-κB and TOPO1 signaling. The tumor suppressor functions of Par-4 can be compromised through different oncogenic pathways. For example, Akt could inhibit Par-4 translocation to the nucleus by phosphorylating Par-4. Furthermore, Fbxo45 interacts with Par-4 in the cytoplasm and mediates its ubiquitination and subsequent proteasomal degradation, leading to cancer cell survival