{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yamada Y"],"funding":["MEXT | Japan Society for the Promotion of Science (JSPS)","Swiss National Science Foundation","Swiss National Science Foundation | nccr - on the move (National Center of Competence in Research - The Migration-Mobility Nexus)"],"pagination":["285"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12182575"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(1)"],"pubmed_abstract":["Although liver kinase B1 (LKB1) has been established as a tumor suppressor kinase, its mechanism of action is incompletely understood. Here we describe a novel nonenzymatic function of LKB1 in cell death induced by Fas/CD95. In BID knockout HeLa cells, inactivation of mitochondrial outer membrane permeabilization (MOMP) prevents Smac-induced inhibition of X-linked inhibitor of apoptosis (XIAP), causing resistance to Fas-induced apoptosis. However, reexpression of LKB1 in those cells naturally deficient for endogenous LKB1 restored apoptosis. Mechanistically, caspase-8 activated by Fas processed LKB1 to a truncated form, tLKB1. Both WT and kinase-inactive LKB1 antagonized XIAP to restore apoptosis, but somatic mutants of LKB1 found in Peutz-Jeghers syndrome (PJS) failed to do so. Thus, in a"],"journal":["Cell death discovery"],"pubmed_title":["Truncated LKB1 nonenzymatically enhances Fas-induced apoptosis by acting as a surrogate of Smac."],"pmcid":["PMC12182575"],"funding_grant_id":["JP21H00268","JP24KJ0428","JP24K02237","JP18J20440","205196","JP24K02173","JP21H02691","310030","310030-205196","JP21H02620"],"pubmed_authors":["Noguchi T","Tokunaga F","Mitsuya M","Yokosawa T","Shimada T","Yamada Y","Schneider P","Matsuzawa A","Oikawa D","Hirata Y","Tsuchida M"],"additional_accession":[]},"is_claimable":false,"name":"Truncated LKB1 nonenzymatically enhances Fas-induced apoptosis by acting as a surrogate of Smac.","description":"Although liver kinase B1 (LKB1) has been established as a tumor suppressor kinase, its mechanism of action is incompletely understood. Here we describe a novel nonenzymatic function of LKB1 in cell death induced by Fas/CD95. In BID knockout HeLa cells, inactivation of mitochondrial outer membrane permeabilization (MOMP) prevents Smac-induced inhibition of X-linked inhibitor of apoptosis (XIAP), causing resistance to Fas-induced apoptosis. However, reexpression of LKB1 in those cells naturally deficient for endogenous LKB1 restored apoptosis. Mechanistically, caspase-8 activated by Fas processed LKB1 to a truncated form, tLKB1. Both WT and kinase-inactive LKB1 antagonized XIAP to restore apoptosis, but somatic mutants of LKB1 found in Peutz-Jeghers syndrome (PJS) failed to do so. Thus, in a","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jun","modification":"2026-05-29T14:29:03.789Z","creation":"2026-04-08T05:03:55.864Z"},"accession":"S-EPMC12182575","cross_references":{"pubmed":["40544190"],"doi":["10.1038/s41420-025-02570-1"]}}