biostudies-literatureKalpongnukul NDevelopment and Promotion of Science and TechnologyChulalongkorn UniversityOffice of the Higher Education CommissionInstitute for the Promotion of Teaching Science and TechnologyThailand Research FundNational Research Council of Thailand2893-2904https://www.ebi.ac.uk/biostudies/studies/S-EPMC9724709biostudies-literatureUnknown21(12)Glioblastoma (GBM) is a devastating primary brain cancer with a poor prognosis. GBM is associated with an abnormal mechanistic target of rapamycin (mTOR) signaling pathway, consisting of two distinct kinase complexes: mTORC1 and mTORC2. The complexes play critical roles in cell proliferation, survival, migration, metabolism, and DNA damage response. This study investigated the aberrant mTORC2 signaling pathway in GBM cells by performing quantitative phosphoproteomic analysis of U87MG cells under different drug treatment conditions. Interestingly, a functional analysis of phosphoproteome revealed that mTORC2 inhibition might be involved in double-strand break (DSB) repair. We further characterized the relationship between mTORC2 and BRISC and BRCA1-A complex member 1 (BABAM1). We demonstratJournal of proteome researchPhosphoproteomic Analysis Defines BABAM1 as mTORC2 Downstream Effector Promoting DNA Damage Response in Glioblastoma Cells.PMC9724709RA62/075026/2015MRG6180215Kaewsapsak PWongkongkathep PPisitkun TChantaravisoot NKalpongnukul NBootsri RAriyachet CfalsePhosphoproteomic Analysis Defines BABAM1 as mTORC2 Downstream Effector Promoting DNA Damage Response in Glioblastoma Cells.Glioblastoma (GBM) is a devastating primary brain cancer with a poor prognosis. GBM is associated with an abnormal mechanistic target of rapamycin (mTOR) signaling pathway, consisting of two distinct kinase complexes: mTORC1 and mTORC2. The complexes play critical roles in cell proliferation, survival, migration, metabolism, and DNA damage response. This study investigated the aberrant mTORC2 signaling pathway in GBM cells by performing quantitative phosphoproteomic analysis of U87MG cells under different drug treatment conditions. Interestingly, a functional analysis of phosphoproteome revealed that mTORC2 inhibition might be involved in double-strand break (DSB) repair. We further characterized the relationship between mTORC2 and BRISC and BRCA1-A complex member 1 (BABAM1). We demonstrat2022-01-01T00:00:00Z2022 Dec2025-04-05T11:53:28.552Z2025-04-05T11:53:28.552ZS-EPMC97247093631565210.1021/acs.jproteome.2c00240