USP8 Recombinant Rabbit mAb (S-3848-146)

USP8 (ubiquitin-specific protease 8) is a deubiquitinating enzyme that primarily functions to cleave and remove ubiquitin chains from substrate proteins, thereby regulating protein stability, signal transduction, and membrane trafficking. This enzyme contains multiple functional domains, including a microtubule-interacting and trafficking (MIT) domain, a catalytic domain, and several SH3-binding motifs, enabling it to interact with various proteins and localize to endosomal membranes. In its classical function, USP8 antagonizes the ubiquitination mediated by HECT-type E3 ligases (such as Nedd4), regulating the endosomal sorting and degradation of membrane receptors such as the epidermal growth factor receptor (EGFR), preventing their entry into the lysosomal pathway, thereby enhancing receptor signaling. Additionally, USP8 participates in maintaining endosomal homeostasis, regulating autophagic flux, and centrosome stability. In terms of disease, gain-of-function mutations in USP8 (particularly missense mutations in the catalytic domain or mutations in the 14-3-3 protein-binding motif) are the most common genetic cause of Cushing's disease (corticotroph adenoma). These mutations lead to increased USP8 protein stability and enhanced deubiquitinating activity, subsequently upregulating EGFR signaling and promoting pro-opiomelanocortin (POMC) expression and excessive ACTH secretion. Furthermore, USP8 is highly expressed in various cancers, where it promotes tumor cell proliferation and drug resistance by stabilizing EGFR, other receptor tyrosine kinases, or anti-apoptotic proteins such as MCL1, making it a potential therapeutic target. Therefore, USP8, as a key regulatory enzyme in the ubiquitination-deubiquitination dynamic balance, plays complex dual roles in endosomal trafficking, cell signaling, and disease development.