SPOP是抑癌基因，编码蛋白是CUL3泛素连接酶复合物中的衔接蛋白，该复合物为泛素化和后续的通过蛋白酶体的降解对底物进行识别。CUL3-SPOP复合物负调节DAXX转录抑制因子，从而影响由DAXX调控的内皮途径基因的表达。约5%的子宫内膜癌和10%的前列腺癌报道了SPOP的体细胞突变。SPOP介导的降解也参与PD-L1的调节。有证据表明，SPOP可能是胶质母细胞瘤、胃癌和结直肠癌中更普遍的肿瘤抑制因子，SPOP表达因肿瘤进展而降低。

SPOP (Speckle-type POZ protein) is an adaptor protein in the CUL3 ubiquitin ligase complex that recognizes substrates for ubiquitination and subsequent degradation via the proteasome. The repertoire of SPOP substrates is not well characterized; however, notable proteins include SRC3, DAXX, H2AFY, AR, BMI1, DEK, ESR1 and TRIM24. The CUL3-SPOP complex negatively regulates the transcriptional repressor DAXX, hence impacting the expression of endothelial pathway genes that are regulated by DAXX. Somatic mutations in SPOP are reported in approximately 5% of endometrial cancers and 10% of prostate cancers. SPOP-mediated degradation has also been implicated in the regulation of PD-L1, a key regulatory immune ligand. SPOP mutations in both endometrial and prostate cancer cluster in conserved residues of the MATH domain important for substrate recognition, suggesting that the mutations either alter substrate recognition or act as a dominant negative to prevent substrate degradation. There is emerging evidence that SPOP may be a more general tumor suppressor in glioblastoma, gastric and colorectal cancers, as SPOP expression is decreased through tumor progression.

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