{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPSMB10 encodes one of the key immunoproteasome β subunits that contributes to the assembly and function of the 20S proteasome. Variants in proteasome‐encoding (PSMB) genes have been investigated in multiple myeloma patients to understand potential impacts on proteasome function and drug resistance, although no direct relationship with bortezomib response was found."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, PSMB10—whose protein product is also designated as MECL‑1 or LMP10—plays a critical role in the antigen processing machinery by generating peptides for major histocompatibility complex (MHC) class I presentation. In carcinoma models, activation of cellular receptors such as CD40 engages NF‑κB and IRF‑1, culminating in the transcriptional upregulation of immunoproteasome subunits including PSMB10. This coordinated regulation ensures proper peptide generation for effective immune surveillance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, PSMB10 expression is dynamically regulated in inflammatory processes. For instance, during angiotensin II–induced retinopathy, upregulation of the LMP10 subunit promotes PTEN degradation and subsequent activation of the AKT/IKK/NF‑κB signaling cascade, thereby contributing to vascular permeability, oxidative stress, and inflammatory damage in the retina. Similar investigations in head and neck carcinomas have evaluated LMP10 as a potential biomarker, underscoring its relevance in both inflammatory and neoplastic contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in immune processing and inflammation, PSMB10/MECL‑1 is modulated by viral factors and targeted gene silencing strategies. Adenovirus E1A, for example, interacts with MECL‑1 to downregulate its expression alongside other immunoproteasome subunits, thereby impairing interferon‐mediated antigen presentation. Furthermore, studies have demonstrated that interferon‑induced incorporation of MECL‑1 into the immunoproteasome is essential for T-cell–mediated immunity, while siRNA‐mediated silencing of inducible subunits—including MECL‑1—offers promising therapeutic avenues for autoimmune and neurodegenerative diseases. Investigations into related ubiquitin ligase complexes further highlight the intricate regulatory networks governing proteasome subunit stability, although these mechanisms are distinct from the antigen‐processing function attributed specifically to PSMB10."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "David I Lichter, Hadi Danaee, Michael D Pickard, et al. 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