{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Manea T"],"funding":["Cancer Research UK","Medical Research Council","The Francis Crick Institute","Wellcome Trust","Engineering and Physical Sciences Research Council"],"pagination":["2457"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10147604"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(1)"],"pubmed_abstract":["Understanding the factors and mechanisms involved in beta-cell development will guide therapeutic efforts to generate fully functional beta cells for diabetes. Neurogenin 3 (NGN3) is the key transcription factor that marks endocrine progenitors and drives beta-cell differentiation. Here we screen for binding partners of NGN3 and identify the deubiquitylating enzyme USP7 as a key regulator of NGN3 stability. Mechanistically, USP7 interacts with, deubiquitinates and stabilizes NGN3. In vivo, conditional knockout of Usp7 in the mouse embryonic pancreas causes a dramatic reduction in islet formation and hyperglycemia in adult mice, due to impaired NGN3-mediated endocrine specification during pancreatic development. Furthermore, pharmacological inhibition of USP7 during endocrine specification "],"journal":["Nature communications"],"pubmed_title":["USP7 controls NGN3 stability and pancreatic endocrine lineage development."],"pmcid":["PMC10147604"],"funding_grant_id":["MR/T015470/1","FC001039","MR/S000011/1","218461/Z/19/Z","EP/T003103/1","CC2015","215138/Z/18/Z"],"pubmed_authors":["Behrens A","Garrone CM","Manea T","Nelson JK","Evans I","Hansson K","Sancho R"],"additional_accession":[]},"is_claimable":false,"name":"USP7 controls NGN3 stability and pancreatic endocrine lineage development.","description":"Understanding the factors and mechanisms involved in beta-cell development will guide therapeutic efforts to generate fully functional beta cells for diabetes. Neurogenin 3 (NGN3) is the key transcription factor that marks endocrine progenitors and drives beta-cell differentiation. Here we screen for binding partners of NGN3 and identify the deubiquitylating enzyme USP7 as a key regulator of NGN3 stability. Mechanistically, USP7 interacts with, deubiquitinates and stabilizes NGN3. In vivo, conditional knockout of Usp7 in the mouse embryonic pancreas causes a dramatic reduction in islet formation and hyperglycemia in adult mice, due to impaired NGN3-mediated endocrine specification during pancreatic development. Furthermore, pharmacological inhibition of USP7 during endocrine specification ","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Apr","modification":"2026-07-14T20:08:41.635Z","creation":"2025-02-19T04:46:20.823Z"},"accession":"S-EPMC10147604","cross_references":{"pubmed":["37117185"],"doi":["10.1038/s41467-023-38146-9"]}}