{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang H"],"funding":["Zhejiang Engineering Research Center of Innovative technologies and diagnostic and therapeutic equipment for urinary system diseases","The National Natural Science Foundation of Zhejiang","The K.C. Wong Magna Fund in Ningbo University","The Ningbo Top Medical and Health Research Program","The Youth Science and Technology Innovation Leader of Ningbo","The National Natural Science Foundation of China","The Ningbo Clinical Research Center for Urological Disease"],"pagination":["e186871"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12016936"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(8)"],"pubmed_abstract":["It is well documented that impaired DNA damage repair (DDR) induces genomic instability that can efficiently increase the sensitivity of prostate cancer (PCa) cells to PARP inhibitors; however, the underlying mechanism remains elusive. Here, we found profound genomic instability in PCa cells with SPOP gene mutations and confirmed the sensitivity of SPOP-mutated PCa cells to olaparib-induced apoptosis. Mechanistically, we identified olaparib-induced CK2-mediated phosphorylation of PIAS1-S468, which in turn mediated SUMOylation of SPOP, thus promoting its E3 ligase activity in the DDR. Moreover, an abnormal CK2/PIAS1/SPOP axis due to SPOP mutations or defects in CK2-mediated phosphorylation of PIAS1, as well as SPOP inhibitor treatment, led to impaired DDR, thus increasing olaparib-induced a"],"journal":["JCI insight"],"pubmed_title":["SPOP mutations increase PARP inhibitor sensitivity via CK2/PIAS1/SPOP axis in prostate cancer."],"pmcid":["PMC12016936"],"funding_grant_id":["32270821","LTGY24H160005","LY24C050001","2022020203","2019A21001","Not Applicable","2023QL052"],"pubmed_authors":["Zheng Z","Kong L","Chai L","Li J","Wu L","Jin X","Lv X","Zhang H","Zhao Y","Liu Y","Liu Z","Yan Z","Cao X","You H","Jin J"],"additional_accession":[]},"is_claimable":false,"name":"SPOP mutations increase PARP inhibitor sensitivity via CK2/PIAS1/SPOP axis in prostate cancer.","description":"It is well documented that impaired DNA damage repair (DDR) induces genomic instability that can efficiently increase the sensitivity of prostate cancer (PCa) cells to PARP inhibitors; however, the underlying mechanism remains elusive. Here, we found profound genomic instability in PCa cells with SPOP gene mutations and confirmed the sensitivity of SPOP-mutated PCa cells to olaparib-induced apoptosis. Mechanistically, we identified olaparib-induced CK2-mediated phosphorylation of PIAS1-S468, which in turn mediated SUMOylation of SPOP, thus promoting its E3 ligase activity in the DDR. Moreover, an abnormal CK2/PIAS1/SPOP axis due to SPOP mutations or defects in CK2-mediated phosphorylation of PIAS1, as well as SPOP inhibitor treatment, led to impaired DDR, thus increasing olaparib-induced a","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Apr","modification":"2026-06-01T12:53:32.873Z","creation":"2025-07-10T03:09:06.858Z"},"accession":"S-EPMC12016936","cross_references":{"pubmed":["40260915"],"doi":["10.1172/jci.insight.186871"]}}