{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kim SY"],"funding":["NICHD NIH HHS","Foundation for the National Institutes of Health","NIMH NIH HHS","NCI NIH HHS","NINDS NIH HHS","U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development"],"pagination":["502-515"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6370889"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(3)"],"pubmed_abstract":["Platinum-based chemotherapies can result in ovarian insufficiency by reducing the ovarian reserve, a reduction believed to result from apoptosis of immature oocytes via activation/phosphorylation of TAp63α by multiple kinases including CHEK2, CK1, and ABL1. Here we demonstrate that cisplatin (CDDP) induces oocyte apoptosis through a novel pathway and that temporary repression of this pathway fully preserves ovarian function in vivo. Although ABL kinase inhibitors effectively block CDDP-induced apoptosis of oocytes, oocytic ABL1, and ABL2 are dispensable for damage-induced apoptosis. Instead, CDDP activates TAp63α through the ATR > CHEK1 pathway independent of TAp63α hyper-phosphorylation, whereas X-irradiation activates the ATM > CHEK2 > TAp63α-hyper-phosphorylation pathway. Furthermore, o"],"journal":["Cell death and differentiation"],"pubmed_title":["Transient inhibition of p53 homologs protects ovarian function from two distinct apoptotic pathways triggered by anticancer therapies."],"pmcid":["PMC6370889"],"funding_grant_id":["P30 CA016058","P50 HD076188","50HD076188","R01 CA154358","R01 NS039475","R01 HD064402","R01 MH115939","R01 NS089662","R01 NS105640","P50HD076188"],"pubmed_authors":["Kim SY","Serna VA","Nair DM","Kurita T","Romero M","Woodruff TK","Koleske AJ"],"additional_accession":[]},"is_claimable":false,"name":"Transient inhibition of p53 homologs protects ovarian function from two distinct apoptotic pathways triggered by anticancer therapies.","description":"Platinum-based chemotherapies can result in ovarian insufficiency by reducing the ovarian reserve, a reduction believed to result from apoptosis of immature oocytes via activation/phosphorylation of TAp63α by multiple kinases including CHEK2, CK1, and ABL1. Here we demonstrate that cisplatin (CDDP) induces oocyte apoptosis through a novel pathway and that temporary repression of this pathway fully preserves ovarian function in vivo. Although ABL kinase inhibitors effectively block CDDP-induced apoptosis of oocytes, oocytic ABL1, and ABL2 are dispensable for damage-induced apoptosis. Instead, CDDP activates TAp63α through the ATR > CHEK1 pathway independent of TAp63α hyper-phosphorylation, whereas X-irradiation activates the ATM > CHEK2 > TAp63α-hyper-phosphorylation pathway. Furthermore, o","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Mar","modification":"2026-07-14T14:55:15.89Z","creation":"2025-04-05T20:37:36.513Z"},"accession":"S-EPMC6370889","cross_references":{"pubmed":["29988075"],"doi":["10.1038/s41418-018-0151-2"]}}