Ubiquitin specific peptidase 32 (USP32)

Ubiquitin specific peptidase 32 (USP32) is a cysteine-type deubiquitinating enzyme that removes ubiquitin from target proteins, thereby regulating their degradation, localization, and function[2][6]. USP32 is active in the cytosol and Golgi apparatus and is involved in multiple cellular pathways, including the positive regulation of mTORC1 signaling via deubiquitination of LAMTOR1[2][6]. It also regulates endosomal and lysosomal trafficking by acting on substrates such as RAB7A[2][3]. USP32 is broadly expressed, with highest levels in testis, cytoplasm, and at the cell membrane[1]. Functionally, USP32 plays essential roles in cell proliferation, cell cycle progression, invasion, migration, and DNA repair, often through stabilization of substrate proteins such as BAG3, and activation of signaling cascades such as the RAF/MEK/ERK pathway in cancers like non-small cell lung cancer (NSCLC)[1]. Its dysregulation or overexpression is associated with poor prognosis in several tumor types, and USP32 is being explored as a potential therapeutic target in oncology[1][7]. No specific clinical drugs are currently approved against USP32, but it represents an emerging area of drug discovery within the class of DUB inhibitors.

Other names

Ubiquitin carboxyl-terminal hydrolase 32Deubiquitinating enzyme 32Renal carcinoma antigen NY-REN-60Ubiquitin thioesterase 32Ubiquitin-specific-processing protease 32NY-REN-60Ubiquitin specific protease 32Ubiquitin thiolesterase 32

Competitive or covalent inhibition of the catalytic domain to block deubiquitinase activity (general for DUB inhibitors, not unique to USP32) Modulation of protein-protein interactions affecting downstream signaling pathways (e.g., interfering with RAF/MEK/ERK pathway activation through BAG3 stabilization)[1]