PIAS1-RAD51 inhibitory peptide

PIAS1-RAD51 inhibitory peptide is a cell-penetrating peptide designed to disrupt the protein-protein interaction between the SUMO E3 ligase PIAS1 and the homologous recombination (HR) repair protein RAD51. Mechanistically, DNA damage triggers ATM-dependent phosphorylation of PIAS1, which enhances its SUMO ligase activity and catalyzes the SUMOylation of RAD51 at lysine residues 70 and 71. This modification stabilizes RAD51 binding to single-stranded DNA, facilitating its retention at damage sites and promoting HR-mediated DNA repair, which contributes to radiotherapy resistance in prostate cancer. By blocking the PIAS1-RAD51 interaction, the inhibitory peptide prevents RAD51 SUMOylation, reduces RAD51 foci formation, suppresses HR repair, and sensitizes tumor cells to radiation. Developed by researchers at Fujian Medical University, the peptide has demonstrated preclinical efficacy in patient-derived organoid (PDO) and xenograft (PDX) models of high-risk, radioresistant prostate cancer, particularly when combined with radiotherapy.

Other names

PIAS1-RAD51 interaction inhibitor peptidePIAS-1-RAD51 interaction inhibitor peptidePIAS 1-RAD51 interaction inhibitor peptideSUMOylation-blocking peptidecell-penetrating PIAS1-RAD51 inhibitory peptide