USP8

Ubiquitin-specific protease 8 (USP8) functions as a deubiquitinating enzyme critical for protein homeostasis by regulating endosomal and lysosomal trafficking^[1]. Mechanistically, USP8 stabilizes multiple receptor tyrosine kinases (RTKs) such as EGFR, c-Met, and Kit, thereby influencing downstream signaling pathways that control cell proliferation, survival, and migration^[2][1]. In disease models, USP8 mutations or overexpression have been implicated in corticotroph pituitary adenomas and multiple myeloma, promoting tumor growth and therapy resistance^[3][1]. Compared with related isoforms like USP7 and USP15, USP8 exhibits specificity for RTK substrates and has distinct effects on plasma and germinal center B-cell populations^[4][1]. Inhibition of USP8 using small-molecule inhibitors such as DUB-IN-2 selectively induces degradation of oncogenic RTKs, disrupts proteostasis, and sensitizes resistant cancer cells to proteasome inhibitors^[2][1]. These characteristics make USP8 a valuable target for experimental applications in cancer research and endocrine disease studies, allowing mechanistic investigation of deubiquitination-dependent signaling and therapeutic intervention strategies^[3][1].