Cullin proteins assemble a large number of RING E3 ubiquitin ligases, participating in the proteolysis through the ubiquitin-proteasome pathway. Two cullin 4 (CUL4) proteins, CUL4A (87 kDa) and CUL4B(104 kDa), have been identified. The two CUL4 sequences are 83% identical. They target certain proteins for degradation by binding protein DDB1 to form a CUL4-DDB1 ubiquitin ligase complex with DDB. They form two individual E3 ligases, DDB1-CUL4ADDB2 and DDB1-CUL4BDDB2 in this process. CUL4A appeared in both the nucleus and the cytosol, suggesting a more complex mechanism for entering the nucleus. CUL4B is localized in the nucleus and facilitates the transfer of DDB1 into the nucleus independently of DDB2.