{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Herzog D"],"funding":["Deutsche Forschungsgemeinschaft","European Research Council"],"pagination":["8613-8623"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9121386"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["144(19)"],"pubmed_abstract":["The tumor suppressor protein <i>fragile histidine triad</i> (Fhit) is known to be associated with genomic instability and apoptosis. The tumor-suppressive function of Fhit depends on the interaction with the alarmone diadenosine triphosphate (Ap<sub>3</sub>A), a noncanonical nucleotide whose concentration increases upon cellular stress. How the Fhit-Ap<sub>3</sub>A complex exerts its signaling function is unknown. Here, guided by a chemical proteomics approach employing a synthetic stable Fhit-Ap<sub>3</sub>A complex, we found that the Fhit-Ap<sub>3</sub>A complex, but not Fhit or Ap<sub>3</sub>A alone, impedes translation. Our findings provide a mechanistic model in which Fhit translocates from the nucleolus into the cytosol upon stress to form an Fhit-Ap<sub>3</sub>A complex. The Fhit-Ap"],"journal":["Journal of the American Chemical Society"],"pubmed_title":["Chemical Proteomics of the Tumor Suppressor Fhit Covalently Bound to the Cofactor Ap<sub>3</sub>A Elucidates Its Inhibitory Action on Translation."],"pmcid":["PMC9121386"],"funding_grant_id":["MA 2288 / 19-1","STE 2517/1-1","ERC-AdG 101019280","101019280"],"pubmed_authors":["Mißun M","Diederichs K","Jansen J","Stengel F","Marx A","Herzog D"],"additional_accession":[]},"is_claimable":false,"name":"Chemical Proteomics of the Tumor Suppressor Fhit Covalently Bound to the Cofactor Ap<sub>3</sub>A Elucidates Its Inhibitory Action on Translation.","description":"The tumor suppressor protein <i>fragile histidine triad</i> (Fhit) is known to be associated with genomic instability and apoptosis. The tumor-suppressive function of Fhit depends on the interaction with the alarmone diadenosine triphosphate (Ap<sub>3</sub>A), a noncanonical nucleotide whose concentration increases upon cellular stress. How the Fhit-Ap<sub>3</sub>A complex exerts its signaling function is unknown. Here, guided by a chemical proteomics approach employing a synthetic stable Fhit-Ap<sub>3</sub>A complex, we found that the Fhit-Ap<sub>3</sub>A complex, but not Fhit or Ap<sub>3</sub>A alone, impedes translation. Our findings provide a mechanistic model in which Fhit translocates from the nucleolus into the cytosol upon stress to form an Fhit-Ap<sub>3</sub>A complex. The Fhit-Ap","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 May","modification":"2026-04-08T17:27:47.407Z","creation":"2024-11-21T02:17:15.21Z"},"accession":"S-EPMC9121386","cross_references":{"pubmed":["35522782"],"doi":["10.1021/jacs.2c00815"]}}