{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lin JF"],"funding":["Hunan Provincial Natural Science Foundation of China","Postdoctoral Science Foundation of China","Guangdong Basic and Applied Basic Research Foundation","National Natural Science Foundation of China","The National Key R&D Program of China","National Natural Science Foundation of China (National Science Foundation of China)","Young Talents Program of Sun Yat-sen University Cancer Center"],"pagination":["263"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11696352"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["Metabolic enzymes perform moonlighting functions during tumor progression, including the modulation of chemoresistance. However, the underlying mechanisms of these functions remain elusive. Here, utilizing a metabolic clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout library screen, we observe that the loss of glutamate-cysteine ligase modifier subunit (GCLM), a rate-limiting enzyme in glutathione biosynthesis, noticeably increases the sensitivity of colorectal cancer (CRC) cells to platinum-based chemotherapy. Mechanistically, we unveil a noncanonical mechanism through which nuclear GCLM competitively interacts with NF-kappa-B (NF-κB)-repressing factor (NKRF), to promote NF-κB activity and facilitate chemoresistance. In response to platinum drug treatment, G"],"journal":["Nature communications"],"pubmed_title":["Nucleus-translocated GCLM promotes chemoresistance in colorectal cancer through a moonlighting function."],"pmcid":["PMC11696352"],"funding_grant_id":["82303306","82373376"],"pubmed_authors":["Liang ZB","Lin JF","Chen DL","Zeng ZL","Huang RZ","Cao F","Han Y","Liu ZX","Yu K","Sheng H","Liao K","Xu RH","Li T","Ju HQ","Li SS","Gao S","Mo HY"],"additional_accession":[]},"is_claimable":false,"name":"Nucleus-translocated GCLM promotes chemoresistance in colorectal cancer through a moonlighting function.","description":"Metabolic enzymes perform moonlighting functions during tumor progression, including the modulation of chemoresistance. However, the underlying mechanisms of these functions remain elusive. Here, utilizing a metabolic clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout library screen, we observe that the loss of glutamate-cysteine ligase modifier subunit (GCLM), a rate-limiting enzyme in glutathione biosynthesis, noticeably increases the sensitivity of colorectal cancer (CRC) cells to platinum-based chemotherapy. Mechanistically, we unveil a noncanonical mechanism through which nuclear GCLM competitively interacts with NF-kappa-B (NF-κB)-repressing factor (NKRF), to promote NF-κB activity and facilitate chemoresistance. In response to platinum drug treatment, G","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jan","modification":"2026-06-02T02:04:18.85Z","creation":"2025-04-05T22:50:01.759Z"},"accession":"S-EPMC11696352","cross_references":{"pubmed":["39747101"],"doi":["10.1038/s41467-024-55568-1"]}}