subunit of IκB is mediated by ubiquitination, and this ubiquitination depends on neddylation. Pevonedistat (MLN4924) inhibits activation of NEDD8, that then inhibits ubiquitination of IκBα, and this inhibits NF-κB translocation to the nucleus. Pevonedistat, through its effects on NF-κB and a target of NF-κB (microRNA-155), prolonged the survival of mice engrafted with leukemic cells. Colorectal cancer Inhibition of NEDD8 activation by pevonedistat was found to induce growth arrest and apoptosis in 16/122 (13%) colorectal cancer (CRC) cell lines. Further analyses in patient-derived tumor xenografts revealed that pevonedistat is effective on poorly differentiated, high-grade mucinous CRC. Interactions NEDD8 has been shown to interact with: Aryl hydrocarbon receptor, NUB1, UBE1C, UBE2M, and UCHL3. References Further reading Human proteins