{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Varineau JE"],"funding":["Massachusetts Institute of Technology","Pew Charitable Trusts","National Cancer Institute","NCI NIH HHS","National Institutes of Health","National Institute of General Medical Sciences","NIGMS NIH HHS","NIH HHS"],"pagination":["dmm050356"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10924232"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(2)"],"pubmed_abstract":["Disruptions in core cellular processes elicit stress responses that drive cell-state changes leading to organismal phenotypes. Perturbations in the splicing machinery cause widespread mis-splicing, resulting in p53-dependent cell-state changes that give rise to cell-type-specific phenotypes and disease. However, a unified framework for how cells respond to splicing perturbations, and how this response manifests itself in nuanced disease phenotypes, has yet to be established. Here, we show that a p53-stabilizing Mdm2 alternative splicing event and the resulting widespread downregulation of metabolic transcripts are common events that arise in response to various splicing perturbations in both cellular and organismal models. Together, our results classify a common cellular response to splici"],"journal":["Disease models & mechanisms"],"pubmed_title":["A common cellular response to broad splicing perturbations is characterized by metabolic transcript downregulation driven by the Mdm2-p53 axis."],"pmcid":["PMC10924232"],"funding_grant_id":["R35GM142634","T32GM007287","P30-CA14051","T32 GM007287","R35 GM142634","P30 CA014051"],"pubmed_authors":["Calo E","Varineau JE"],"additional_accession":[]},"is_claimable":false,"name":"A common cellular response to broad splicing perturbations is characterized by metabolic transcript downregulation driven by the Mdm2-p53 axis.","description":"Disruptions in core cellular processes elicit stress responses that drive cell-state changes leading to organismal phenotypes. Perturbations in the splicing machinery cause widespread mis-splicing, resulting in p53-dependent cell-state changes that give rise to cell-type-specific phenotypes and disease. However, a unified framework for how cells respond to splicing perturbations, and how this response manifests itself in nuanced disease phenotypes, has yet to be established. Here, we show that a p53-stabilizing Mdm2 alternative splicing event and the resulting widespread downregulation of metabolic transcripts are common events that arise in response to various splicing perturbations in both cellular and organismal models. Together, our results classify a common cellular response to splici","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-07-15T11:57:46.242Z","creation":"2026-07-04T03:12:09.336Z"},"accession":"S-EPMC10924232","cross_references":{"pubmed":["38426258"],"doi":["10.1242/dmm.050356"]}}