Dissecting the Functional Role of the TRIM8 Protein on Cancer Pathogenesis

SIMPLE SUMMARY: The tripartite motif (TRIM) gene family is a large group of E3 ubiquitin ligase proteins that can also have proteasome-independent functions. This review summarizes the structural organization, the biological functions and the mechanisms involved in cancer pathogenesis of TRIM proteins. Furthermore, this paper focuses on TRIM8, a member of the TRIM family proteins, describing its role both as a tumor suppressor and as an oncogene. ABSTRACT: TRIM/RBCC are a large family of proteins that include more than 80 proteins, most of which act as E3 ligases and catalyze the direct transfer of Ubiquitin, SUMO and ISG15 on specific protein substrates. They are involved in oncogenesis processes and in cellular immunity. On this topic, we focus on TRIM8 and its multiple roles in tumor pathologies. TRIM8 inhibits breast cancer proliferation through the regulation of estrogen signaling. TRIM8 downregulation in glioma is involved in cell proliferation, and it is related to patients’ survival. Several studies suggested that TRIM8 regulates the p53 suppressor signaling pathway: it is involved in the NF-kB pathway (Nuclear Factor kappa light- chain-enhancer of activated B cells) and in STAT3 (Signal Transducer and Activator of Transcription 3) of the JAK-STAT pathway. In this review, we summarize how the association between these different pathways reflects a dual role of TRIM8 in cancer as an oncogene or a tumor suppressor gene.