CUL3 and neoplasm: Importantly, Speckle-type POZ protein (SPOP) acts as a tumor suppressor through its function as a substrate receptor of the Cullin 3 (CUL3)-based ubiquitin ligase3–6 and directs ubiquitin-proteasomal degradation of key regulators, (e.g., AR, SRC3, TRIM24, and DEK)7–10.