Novel insights into the SPOP E3 ubiquitin ligase: From the regulation of molecular mechanisms to tumorigenesis

Ubiquitin-mediated protein degradation is the primary biological process by which protein abundance is regulated and protein homeostasis is maintained in eukaryotic cells. Speckle-type pox virus and zinc finger (POZ) protein (SPOP) is a typical substrate adaptor of the Cullin 3-RING ligase (CRL3) family; it serves as a bridge between the Cullin 3 (Cul3) scaffold protein and its substrates. In recent years, SPOP has received increasing attention because of its versatility in its regulatory pathways and the diversity of tumor types involved. Mechanistically, SPOP substrates are involved in a wide range of biological processes, and abnormalities in SPOP function perturb downstream biological processes and promote tumorigenesis. Additionally, liquid-liquid phase separation (LLPS), a potential mechanism of membraneless organelle formation, was recently found to mediate the self-triggered colocalization of substrates with higher-order oligomers of SPOP. Herein, we summarize the structure of SPOP and the specific mechanisms by which it mediates the efficient ubiquitination of substrates. Additionally, we review the biological functions of SPOP, the regulation of SPOP expression, the role of SPOP in tumorigenesis and its therapeutic value.

Automated summary

Ubiquitin-mediated protein degradation is a crucial process for maintaining protein homeostasis in eukaryotic cells. SPOP, as a substrate adaptor of the CRL3 family, has garnered attention for its versatility in regulatory pathways and involvement in various tumor types. Abnormalities in SPOP can disrupt downstream biological processes and promote tumorigenesis, while liquid-liquid phase separation may play a role in the interaction between SPOP and its substrates.