{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tiek D"],"funding":["National Institute of Neurological Disorders and Stroke","National Institutes of Health National Cancer Institute","NIA NIH HHS","NINDS NIH HHS","NCI NIH HHS"],"pagination":["111769"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11821397"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["28(2)"],"pubmed_abstract":["Drug resistance is a major barrier to cancer therapies and remains poorly understood. Recently, non-mutational mechanisms of drug resistance have been proposed where a more plastic metabolic response can play a major role. Here, we show that upon drug resistance, glioblastoma (GBM) cells have increased oxidative stress, mitochondria function, and protein aggregation. Gamma (γ)-glutamylcyclotranserase (GGCT), an enzyme in the γ-glutamyl cycle for glutathione production, located on chromosome 7 which is commonly amplified in GBM is also increased upon resistance. We further observe that the byproduct of GGCT-pyroglutamic acid-can bind aggregating proteins and that genetic and pharmacological inhibition of GGCT prevents protein aggregation. Finally, we found increased protein aggregation, GGC"],"journal":["iScience"],"pubmed_title":["Oxidative stress induced protein aggregation via GGCT produced pyroglutamic acid in drug resistant glioblastoma."],"pmcid":["PMC11821397"],"funding_grant_id":["R21 NS126810","R21 NS122375","P50 CA221747","K99 CA279896","P30 AG072977","R01 NS125318","R01 NS133160","K00 CA234799","R01 NS115403"],"pubmed_authors":["Cheng SY","Miska J","Hu B","Vassar R","Tiek D","Jamshidi P","Wu R","Horbinski C","Iglesia R","McCortney K","Castellani R","Song X","Yu X","Catezone A","Walshon J"],"additional_accession":[]},"is_claimable":false,"name":"Oxidative stress induced protein aggregation via GGCT produced pyroglutamic acid in drug resistant glioblastoma.","description":"Drug resistance is a major barrier to cancer therapies and remains poorly understood. Recently, non-mutational mechanisms of drug resistance have been proposed where a more plastic metabolic response can play a major role. Here, we show that upon drug resistance, glioblastoma (GBM) cells have increased oxidative stress, mitochondria function, and protein aggregation. Gamma (γ)-glutamylcyclotranserase (GGCT), an enzyme in the γ-glutamyl cycle for glutathione production, located on chromosome 7 which is commonly amplified in GBM is also increased upon resistance. We further observe that the byproduct of GGCT-pyroglutamic acid-can bind aggregating proteins and that genetic and pharmacological inhibition of GGCT prevents protein aggregation. Finally, we found increased protein aggregation, GGC","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Feb","modification":"2026-06-02T20:03:26.033Z","creation":"2025-04-07T07:54:01.816Z"},"accession":"S-EPMC11821397","cross_references":{"pubmed":["39949960"],"doi":["10.1016/j.isci.2025.111769"]}}