Small ubiquitin-like modifier 1 (SUMO1) (SUMO1)

Small ubiquitin-like modifier 1 (SUMO1) is a member of the SUMO family of proteins that are covalently attached to lysine residues of target proteins through an enzymatic cascade involving E1, E2, and E3 enzymes (UniProt P63165). Unlike ubiquitination, SUMOylation primarily regulates protein function, localization, and stability rather than promoting proteasomal degradation (PubMed: 28233442). SUMO1 is essential for nuclear-cytoplasmic trafficking, transcriptional control, and maintaining genomic integrity through DNA repair pathways (PubMed: 30546054). In oncology, SUMO1 is frequently overexpressed, contributing to the stabilization of oncoproteins and promoting tumor cell survival and metastasis (PubMed: 31434881). Conversely, in cardiovascular disease, impaired SUMOylation of SERCA2a is linked to heart failure, leading to the development of SUMOylation activators like N106 as potential therapies (PubMed: 21903908). Current pharmacological efforts focus on small molecule inhibitors like Subasumstat (TAK-981) and Ginkgolic acid to disrupt these pathways in cancer, though the broad substrate range of SUMO1 presents challenges for therapeutic selectivity (PubMed: 25535191, PubMed: 32612152).

Other names

SUMO-1SentrinSMT3 homolog 3SMT3H3Ubiquitin-like protein SMT3CGAP-modifying protein 1GMP1PIC1

Small molecule inhibitors typically target the SUMO-activating enzyme (E1) to prevent the formation of the E1-SUMO thioester complex, or they may bind directly to SUMO1 to block its interaction with E2 conjugating enzymes (Ubc9), thereby inhibiting the covalent attachment of SUMO1 to target proteins (PubMed: 19233848, PubMed: 21106740).