Identification of Novel Substrates and Binding Partners of Speckle-Type POZ Protein Adapter from Cullin3-Ring E3 Ubiquitin Ligase Complex

Speckle type POZ protein (SPOP) is a ubiquitin E3 ligase protein adapter found to be highly associated with prostate cancer. SPOP prostate cancer mutations were identified to be located within the Meprin and TRAF- C homology (MATH) domain of the protein, which is responsible for substrate recognition and interaction. This study focuses on identifying novel substrates/ binding partners of SPOP and characterizing their involvement in cancer initiation and progression. Due to the high sequence and structural similarity to the MATH domain of Ubiquitin- Specific Protease 7 (USP7) it is possible that there are many overlapping substrates/interacting partners between these two proteins. Eleven novel cellular and viral proteins that interact with SPOP were identified. The cellular proteins were shown to be destabilized upon SPOP over expression. Prostate cancer SPOP mutants showed loss of interaction with their substrates. These novel SPOP substrates/ binding partners bring insight into its involvement in cellular pathways and cancer development.