TRIM25: A central factor in breast cancer

Figure 1 TRIM25 is an E3-ligase common for interferon-stimulated gene 15 and ubiquitin proteins. A: The ISGylation system; B: The Ubiquitination system. The ISGylation system and the ubiquitination system are similar, however, the ubiquitination system has more than 600 E3 ligases and the ISGyaltion system has three E3 ligases. Interestingly, both systems have in common the E3 ligase tripartite motif containing 25. ISG15: Interferon-stimulated gene 15; DUBs: Ubiquitin-proteasome system; Ub: Ubiquitin; USP18: Ubiquitin-specific protease 18.

Figure 2 Structure of TRIM25. A: Crystal structure of the human TRIM25 coiled-coil and PRYSPRY domains. (DNA sequence retrieved from NCBI. Gene, https://www.ncbi.nlm.nih.gov/gene/7706#gene-expression 21/01/21, and 3D model created with Swiss Model: https://swissmodel.expasy.org/); B: Schematic representation of TRIM25, including the conserved RING, B boxes (B1 and B2), the coiled-coil domain and the C-terminal variable domain (CTD) PRY-SPRY; C: RING and CTD domains bind to the ubiquitin-loaded E2 and the substrate, respectively. Consequently, both molecules get closer, therefore favoring substrate ubiquitination.

Figure 3 Structure of TRIM25 gene and its regulation. The structure of the TRIM25 gene is shown in (A) Regulation of TRIM25 expression by ERα, (B) miRNA-3614-3p, and IGF2BP3 through its 3´UTR region.