Analysis of hepatocarcinogenesis due to monoubiquitylation of gankyrin that is one of the proteasome-interacting proteins

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Gankyrin is monoubiquitylated at specific lysine residue posttranslationally. However, other ubiquitin like modifiers, that is, NEDD8, SUMO1-4, ISG15, or URM1, does not bind to gankyrin. Monoubiquitylation of oncogenic gankyrin induces hepatic cell transformation more stimulatedly than wild type nonmodified gankyrin posttranslationally. In hepatoma cell lines, monoubiquitylated gankyrin binds to S6 ATPase and MDM2. Nevertheless, monoubiquitylated gankyrin targets more effectively pRB than p53 toward MDM2 E3 lubiquitin ligase activity. Some of gankyrin monoubiquitylation systems consisting of E1, E2, E3, E4, and DUB will become targets of anti-cancer drugs.