{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Liu Y"],"funding":["NIDDK NIH HHS","NHLBI NIH HHS","U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","CSRD VA"],"pagination":["298-306"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8529588"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(3)"],"pubmed_abstract":["The adenosine monophosphate (AMP)-activated protein kinase (Ampk) is a central regulator of metabolic pathways, and increasing Ampk activity has been considered to be an attractive therapeutic target. Here, we have identified an orphan ubiquitin E3 ligase subunit protein, Fbxo48, that targets the active, phosphorylated Ampkα (pAmpkα) for polyubiquitylation and proteasomal degradation. We have generated a novel Fbxo48 inhibitory compound, BC1618, whose potency in stimulating Ampk-dependent signaling greatly exceeds 5-aminoimidazole-4-carboxamide-1-β-ribofuranoside (AICAR) or metformin. This compound increases the biological activity of Ampk not by stimulating the activation of Ampk, but rather by preventing activated pAmpkα from Fbxo48-mediated degradation. We demonstrate that, consistent w"],"journal":["Nature chemical biology"],"pubmed_title":["A Fbxo48 inhibitor prevents pAMPKα degradation and ameliorates insulin resistance."],"pmcid":["PMC8529588"],"funding_grant_id":["R01 DK119627","R35 HL139860","UH3 HL123502","P01 HL114453","R01 HL098174","T32 HL110849","R01 HL097376","HL081784","I01 CX000105","R01 HL096376","R01 HL081784","R01 HL133184","R01 HL142777"],"pubmed_authors":["O'Donnell CP","Chen BB","Huckestein BR","Monga SP","Mallampalli RK","Nguyen MK","Jiang Y","Liu Y","Jurczak MJ","Lin B","Finkel T","Lear TB","Chen Y","Tuncer F","Larsen MB","Kennerdell JR"],"additional_accession":[]},"is_claimable":false,"name":"A Fbxo48 inhibitor prevents pAMPKα degradation and ameliorates insulin resistance.","description":"The adenosine monophosphate (AMP)-activated protein kinase (Ampk) is a central regulator of metabolic pathways, and increasing Ampk activity has been considered to be an attractive therapeutic target. Here, we have identified an orphan ubiquitin E3 ligase subunit protein, Fbxo48, that targets the active, phosphorylated Ampkα (pAmpkα) for polyubiquitylation and proteasomal degradation. We have generated a novel Fbxo48 inhibitory compound, BC1618, whose potency in stimulating Ampk-dependent signaling greatly exceeds 5-aminoimidazole-4-carboxamide-1-β-ribofuranoside (AICAR) or metformin. This compound increases the biological activity of Ampk not by stimulating the activation of Ampk, but rather by preventing activated pAmpkα from Fbxo48-mediated degradation. We demonstrate that, consistent w","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2025-04-07T00:10:50.803Z","creation":"2025-04-04T19:44:56.101Z"},"accession":"S-EPMC8529588","cross_references":{"pubmed":["33495648"],"doi":["10.1038/s41589-020-00723-0"]}}