{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Bhatt S"],"funding":["NIAAA NIH HHS","NCI NIH HHS","NIGMS NIH HHS"],"pubmed_abstract":["Cyclic adenosine monophosphate (cAMP) signaling is a major stimulus for lipid and glucose catabolism, yet catabolic processes like these can also coordinate with lysosome-dependent degradation. However, the impact of cAMP signaling on lysosomal dynamics remains unclear. Transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, is regulated by stimulus-dependent nuclear-cytoplasmic shuttling through a variety of phosphorylation events. Here, we find that elevating intracellular cAMP with forskolin and IBMX induces rapid nuclear import of TFEB-GFP within 30 minutes and coincides with a transient upregulation of TFEB target lysosome genes. By 8 hours, TFEB returns to the cytoplasm, accompanied by transcriptional downregulation. Inhibition of cAMP-dependent protein kinase A (PKA) using H89 did not block nuclear import but unexpectedly caused sustained nuclear accumulation, indicating that PKA promotes TFEB nuclear export. Consistent with this, phosphoproteomic profiling revealed increased phosphorylation of a PKA-consensus motif (RRxS) during the export phase. These findings suggest that cAMP-PKA signaling plays a novel role in temporally \"tuning\" lysosomal gene expression by regulating TFEB nuclear-cytoplasmic shuttling."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2025.11.24.690233"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12697359"],"repository":["biostudies-literature"],"pubmed_title":["cAMP promotes acute lysosome biogenesis through TFEB nuclear import-export dynamics."],"pmcid":["PMC12697359"],"funding_grant_id":["R35 GM150801","R21 CA279878","R00 AA026877"],"pubmed_authors":["Schott MB","Woods N","Rozeveld CN","Abbas Zaidi MA","Bhatt S"],"additional_accession":[]},"is_claimable":false,"name":"cAMP promotes acute lysosome biogenesis through TFEB nuclear import-export dynamics.","description":"Cyclic adenosine monophosphate (cAMP) signaling is a major stimulus for lipid and glucose catabolism, yet catabolic processes like these can also coordinate with lysosome-dependent degradation. However, the impact of cAMP signaling on lysosomal dynamics remains unclear. Transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, is regulated by stimulus-dependent nuclear-cytoplasmic shuttling through a variety of phosphorylation events. Here, we find that elevating intracellular cAMP with forskolin and IBMX induces rapid nuclear import of TFEB-GFP within 30 minutes and coincides with a transient upregulation of TFEB target lysosome genes. By 8 hours, TFEB returns to the cytoplasm, accompanied by transcriptional downregulation. Inhibition of cAMP-dependent protein kinase A (PKA) using H89 did not block nuclear import but unexpectedly caused sustained nuclear accumulation, indicating that PKA promotes TFEB nuclear export. Consistent with this, phosphoproteomic profiling revealed increased phosphorylation of a PKA-consensus motif (RRxS) during the export phase. These findings suggest that cAMP-PKA signaling plays a novel role in temporally \"tuning\" lysosomal gene expression by regulating TFEB nuclear-cytoplasmic shuttling.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-03T03:16:19.051Z","creation":"2026-06-03T03:10:47.184Z"},"accession":"S-EPMC12697359","cross_references":{"pubmed":["41394755"],"doi":["10.1101/2025.11.24.690233"]}}