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Background: SCCRO3/DCUN1D3 is proposed to function as a tumor suppressor. However, the mechanisms are not well defined. Results: SCCRO3 inhibits SCCRO-promoted nuclear translocation and neddylation of cullins by sequestering them to the cell membrane. Conclusion: SCCRO3 putatively functions as a tumor suppressor by antagonizing the activity of SCCRO. Significance: Understanding how SCCRO and its family members cooperatively regulate cullin neddylation is important for neddylation-targeted cancer therapy.

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