ABSTRACT Ubiquitination is a critical post‐translational modification that regulates protein stability, signalling pathways, and cellular homoeostasis. Increasing evidence shows that oncogenic viruses exploit the host ubiquitin system to promote viral persistence, immune evasion, and malignant transformation. Among the various host factors targeted, deubiquitinating enzymes (DUBs) play a pivotal role because they reverse ubiquitination, thereby regulating the stability, localization, and activity of key signalling proteins. Ubiquitin‐specific peptidase 10 (USP10) has emerged as a particularly critical DUB in the context of viral tumourigenesis, functioning as a molecular rheostat that balances tumour suppression and oncogenic progression. The dysregulation of USP10 by viral oncoproteins facilitates a dual assault on the host: the subversion of innate immune sensors, specifically the RIG‐I, MAVS, and cGAS‐STING pathways, and the evasion of adaptive immune surveillance through the stabilisation of immune checkpoints, such as PD‐L1, and the disruption of MHC‐I antigen presentation. This comprehensive analysis explores the biochemical architecture of USP10, its paradoxical roles in cancer, and the specific mechanisms through which oncogenic viruses exploit this enzyme to drive malignancy and immune escape.
Li et al. (Thu,) studied this question.