Speckle-type POZ protein (SPOP)

Speckle-type POZ protein (SPOP) is an adaptor protein for cullin-3 based E3 ubiquitin ligase complexes, encoded by the SPOP gene in humans[1][6]. It contains an N-terminal MATH (Meprin and TRAF-C homology) domain for substrate recognition and a C-terminal BTB/POZ domain for dimerization and interaction with Cullin-3, enabling the ubiquitination and degradation of multiple protein substrates[2][6][8]. SPOP regulates cellular processes including transcriptional repression, DNA damage response, and maintenance of genome stability[2]. It acts as a tumor suppressor, with mutations frequently found in prostate, renal, and endometrial cancers, particularly affecting the substrate-binding MATH domain[1][2][4][8]. SPOP’s functional repertoire includes targeting oncoproteins (such as DAXX, BRMS1, GLI2/3, macroH2A1, and others) for degradation, modulating various cancer-relevant pathways[6][8]. No approved drugs target SPOP directly, but it has significant interest as a cancer biomarker and therapeutic target due to its mutational landscape and central roles in proteostasis and tumor suppression[2][4][6][8].

Other names

BTBD32TEF2NEDMIDFNSDVS1NSDVS2NEDMACEspeckle type BTB/POZ protein

Modulation of ubiquitination and proteasomal degradation of oncogenic and regulatory proteins[2][4][6][8] Dominant-negative effects through SPOP mutations in cancer[4][8]