Site-Specific Nanobody Inhibitors of the Proteasomal Deubiquitinase UCH37.

ABSTRACT: Dysregulation of the ubiquitin (Ub) proteasome system (UPS) is linked to numerous human diseases, making its components, particularly deubiquitinases (DUBs), attractive therapeutic targets. UCH37 (also known as UCHL5), a proteasomal DUB, plays roles in protein degradation, DNA repair, and transcription and is overexpressed in several cancers. Despite its relevance, the precise functions of UCH37 within the proteasome and the INO80 chromatin remodeling complex remain unclear. Current small-molecule inhibitors exhibit broad, off-target effects, limiting their utility both therapeutically and as probes for UCH37 function. Here, we report the development of highly potent, selective nanobody-based inhibitors for UCH37. Using yeast surface display, we generated nanobodies targeting distinct Ub-b

SUBMITTER: Li Y 

PROVIDER: S-EPMC12363867 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature