Mutations in SPOP and the resulting dysregulation of this proteostatic pathway play causative roles in the pathogenesis of prostate and endometrial cancers, whereas overexpression and mislocalization are associated with kidney cancer.
Genomic analysis revealed that SPOP somatic mutations are found in a subset of endometrial cancers, suggesting that these mutations act as oncogenic drivers of this gynecologic malignancy.
Here we analyzed changes in the ubiquitin landscape induced by endometrial cancer-associated SPOP mutations and identified BRD2, BRD3 and BRD4 proteins (BETs) as SPOP-CUL3 substrates that are preferentially degraded by endometrial cancer-associated SPOP mutants.
Speckle-type POZ (pox virus and zinc finger protein) protein (SPOP) is an E3 ubiquitin ligase adaptor protein that is frequently mutated in prostate and endometrial cancers.