Analysis of Ubiquitination Mediated by LLPS in Cancers

The ubiquitin-proteasome system is the main enforcer of protein degradation in eukaryotic cells, regulating almost all biological processes in cells. Dysregulation of ubiquitin-mediated proteasomal degradation has emerged as an important mechanism in the pathogenesis of many cancers. The spotted poxvirus and zinc finger (POZ) protein (SPOP) serves as a substrate articulator for the cullin3-RING ubiquitin ligase (CRL3) and controls the cellular persistence of various protein substrates for hormone signaling, epigenetic control, and cell cycle regulation. In recent years, SPOP has received increasing attention because of the diversity of its regulatory pathways and the diversity of tumor types involved. Therefore, understanding the molecular mechanisms underlying normal SPOP function and the causes of SPOP-mediated tumorigenesis is critical for the ultimate therapeutic targeting of SPOP and other related pathways.

Fig. 1. Possibilities for therapeutic interventions in SPOP-related cancers. (Cuneo MJ, et al., 2019)

Customized Services

Given the multivalent interactions between substrates and SPOP oligomers, biomolecular condensates associated with SPOP are formed by liquid-liquid phase separation (LLPS). Our experts are committed to studying SPOP/substrate phase separation. CD BioSciences offers specialized services to analyze the function and role of SPOP substrates in different tumor types, providing a theoretical basis for further studies of tumorigenic mechanisms and anti-cancer therapies. The SPOP substrates and related tumor types that we can analyze are as follows:

• AR, TRIM24, HIPK2, 53BP1, PD-L1, Gli3, DEK, ERG, DDIT3, Nanog, Cdc20, CYCLIN E1, INF2, EglN2, ATF2, FASN, Caprin1, 17βHSD4, ITCH, GLP, CDCA5, PDK1 (Prostate cancer)
• ERα (Endometrial and breast cancer)
• PR, Breast cancer (Breast cancer)
• SRC-3 (Prostate and breast cancer) 
• SETD2 (Kidney cancer)
• Gli2 (Kidney, gastric and colorectal cancer)
• MyD88 (Diffused large B-cell lymphoma)
• FADD, SIRT2 (Lung cancer)
• SENP7 (Prostate and liver cancer)
• BRD2/3/4 (Prostate and endometrial cancer)
• C-MYC (Prostate and breast cancer)
• DHX9 (Choriocarcinoma)     
• PTEN, DUSP7, Daxx (Kidney cancer)     
• HDAC6, FLI-1 (Colorectal cancer)
• SLC7A1 (Hepatoblastoma)

In addition to the comprehensive analysis of the function and role of SPOP substrates in different tumor types. Our technical team our technical team is commmitted to developing SPOP-mediated phase separation as an effective therapeutic strategy for the treatment of drug-resistant cancers. Our lab has a cutting-edge platform of Protein Hydrolysis Targeted Chimeras (PROTACs) technology that enables the recruitment of ubiquitin ligases to key oncogenic substrates for catalytic ubiquitination and subsequent turnover of chimeric small molecules. This inhibitor can be used in cancers with functionally acquired SPOP lesions due to mutation, amplification or mislocalization.

Combining proteomics, transcriptomics, imaging, genetics, epidemiology and computer data, CD BioSciences aims to analyze the role of SPOP in different tumor types and the regulatory control of SPOP gene expression, to help our clients develop promising therapeutic targets for cancer treatment. Our services are widely used in preclinical research in cancer biology, diagnosis and treatment. If you are interested in our services, please feel free to contact us.