SPOP and cancer: In accordance with a previous study showing that cancer-associated SPOP mutants function as dominant-negative variants to deregulate their substrates [12], we found that co-expression of the SPOP mutant markedly reduced the interaction between SPOP-WT and BRAF (Fig. 4g), resulting in the suppression of wild-type SPOP-mediated BRAF ubiquitination (Fig. 4h).