The emerging role of speckle-type POZ protein (SPOP) in cancer development.

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. All the cancer-associated SPOP mutations reported to date are clustered in the meprin and TRAF (Tumor necrosis factor receptor-associated factor) homology (MATH) domain, presumably affecting substrate binding. SPOP mutations in prostate cancer are mutually exclusive with the ETS (Erythroblast transformation-specific) family gene rearrangements and define a distinct molecular subclass of prostate cancer. SPOP mutations contribute to prostate cancer development by altering the steady-state levels of key components in the androgen-signaling pathway.