Sentrin-specific protease 8 (SENP8)

Sentrin-specific protease 8 (SENP8) is a cysteine protease enzyme that primarily catalyzes the processing and removal (deneddylation) of NEDD8—a ubiquitin-like posttranslational modifier—from substrate proteins, especially cullin-RING ligases (CRLs) and components of the NEDD8 pathway such as Ubc12[1][2][3]. SENP8 is required for proper activation of CRLs, maintenance of cell cycle progression (notably the G1/S transition), and overall protein homeostasis in cells[1]. Loss or dysfunction of SENP8 leads to accumulation of aberrantly neddylated proteins, defective proteostasis, dysregulated cell cycle progression, and can contribute to tumorigenic phenotypes[1]. The enzyme is considered a potential therapeutic target due to its central role in regulating protein turnover and cell division. SENP8 is encoded by the SENP8 gene (HGNC:22992, UniProtKB:Q96LD8) and is known by multiple names including DEN1, NEDP1, and PRSC2[2][3]. Alterations in SENP8 function have been implicated in diseases such as cancer and neurodevelopmental disorders[1][4].

Other names

DEN1NEDP1PRSC2NEDD8-specific protease 1SUMO peptidase family member, NEDD8 specificSUMO/sentrin peptidase family member, NEDD8 specific

Deneddylation: cleavage of NEDD8 from substrate proteins (mainly cullins, e.g., CUL1, CUL5, Ubc12); Controls substrate turnover by regulating cullin-RING E3 ligase activity