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Furthermore, protein stability and cell viability assays using two distinct proteasome inhibitor anticancer drugs, the 20S proteasome inhibitor bortezomib and the ubiquitin activating enzyme E1 inhibitor TAK-243, which show that upregulation of the NRF3-POMP axis leads to ubiquitin-independent proteolysis of p53 and Rb, and to impaired sensitivity to bortezomib, but not TAK-243. More importantly, the NRF3-POMP axis supports tumorigenesis and metastasis, with higher NRF3/POMP expression correlating with poor prognosis in patients with color