Sentrin-specific protease 1 (SENP1)

Sentrin-specific protease 1 (SENP1) is a cysteine protease enzyme responsible for processing small ubiquitin-like modifier (SUMO) precursors to their mature forms and for deconjugating SUMO from target proteins, a process called deSUMOylation[1][3][4][5]. SENP1 functions primarily in the nucleus but can also localize to the cytoplasm and nuclear pore complex[2][5]. It contains a conserved C-terminal catalytic domain and a variable N-terminal domain that governs subcellular localization and substrate specificity[1][3][4]. SENP1 regulates critical processes including transcription, the cell cycle, apoptosis, immune cell differentiation, and angiogenesis by modulating the SUMOylation state of various substrates, including transcription factors (such as HIF1α and Blimp-1), signaling proteins, and components of the nuclear pore complex[2][4][5]. SENP1 is overexpressed in various cancers and is implicated in tumor progression, metastasis, and vascularization, making it a promising and actively researched therapeutic target in oncology[4][5]. However, due to its essential cellular roles, targeting SENP1 raises challenges regarding selectivity and safety.

Other names

Sentrin-specific protease 1SUMO specific peptidase 1Sentrin/SUMO-specific protease SENP1SuPr-2SUMO1/sentrin specific peptidase 1SUMO1/sentrin specific protease 1

SENP1 inhibitors generally act by blocking the deSUMOylation activity, leading to accumulation of SUMOylated proteins and disruption of processes such as transcription, cell cycle, and protein stability relevant for tumor growth and proliferation[4].