SPOP and neoplasm: Thus, while CDK4/6 phosphorylation of SPOP induces PD-L1 degradation through the Cullin3SPOP E3 ligase [29], its phosphorylation of pRB, dissociates this tumor suppressor from activating-E2Fs, leading to transcriptional activation of CD274 (PD-L1) and the generation of new PD-L1 proteins, with a net increase in PD-L1 level.