|University of Cape Town
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Includes abstract. Defective in Cullin Neddylation 1 Domain Containing 1 (DCUN1D1) is an E3 ligase for the post translational process, neddylation. Neddylation is similar and runs in parallel to the ubiquitin proteasome pathway. Although established as an oncogene in various squamous cell carcinomas, the role of DCUN1D1 in prostate cancer has not been explored and it could be a novel drug target for prostate cancer treatment. We investigated the role of DCUN1D1 in prostate cancer. The expression of DCUN1D1 was evaluated in prostate cancer cell lines and human tissue samples and its effect on tumourigenesis was tested using proliferation, migration, apoptosis and in vivo tumour growth assays. Microarray analysis and the connectivity map database were used to determine the signalling pathways responsible for its mechanism of action and to identify compounds specific for DCUN1D1 to inhibit prostate cancer growth.