Fig 1: FUS is a ubiquitin substrate of CRL4BDTL E3 ligase.A Structural model of CRL4B E3 ligase. B FUS protein level in DDB1-knockdown cells. Huh7 and LM3 cells were transfected with control or DDB1 siRNA for 72 h and then harvested for western blotting analysis. C FUS protein level in RBX1-knockdown cells. Huh7 and LM3 cells were transfected with control or RBX1 siRNA for 72 h and then harvested for western blotting analysis. D FUS protein level in DCAFs-knockdown Huh7 cells. Huh7 cells were transfected with control or DCAF siRNAs for 72 h and then harvested for western blotting analysis. E Half-life of FUS in DTL-knockdown cells. Huh7 cells were transfected with control or DTL siRNA for 72 h and then treated with 50 μg/mL CHX at the indicated time points before being subjected to western blotting analysis. FUS protein expression was quantified using ImageQuant TL software, with levels normalized to that of β-actin for comparison (mean ± SD, n = 3). F The interaction among CUL4B, DTL, DDB1, RBX1, and FUS. Vectors encoding Flag-tagged CUL4B were transfected into Huh7 cells. Cells were then subjected to immunoprecipitation with anti-Flag M2 affinity resin and western blotting analysis. G, H Molecular docking model of CRL4BDTL and FUS based on AlphaFold3 protein prediction. I Root Mean Square Deviation (RMSD) of CRL4BDTL-FUS complex structure during 100 ns MD simulation. J Root Mean Square Fluctuation (RMSF) of CRL4BDTL-FUS complex residues during 100 ns MD simulation. K Radius of Gyration (RG) of CRL4BDTL-FUS complex structures during 100 ns MD simulation. Two-tailed, unpaired t-test was used for (E). Data are presented as the mean ± standard deviation derived from a minimum of three independent experiments. Statistical significance was assessed using the appropriate testing methods, with **p < 0.01 denoting levels of significance.