{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Amici DR"],"funding":["American Cancer Society","HHS | NIH | National Institute of General Medical Sciences","NIA NIH HHS","HHS | NIH | National Cancer Institute","NCI NIH HHS","HHS | NIH | National Institute on Aging","NIH HHS","NIGMS NIH HHS"],"pagination":["e202302370"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10921065"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(5)"],"pubmed_abstract":["The recently discovered HAPSTR1 protein broadly oversees cellular stress responses. This function requires HUWE1, a ubiquitin ligase that paradoxically marks HAPSTR1 for degradation, but much about this pathway remains unclear. Here, leveraging multiplexed proteomics, we find that HAPSTR1 enables nuclear localization of HUWE1 with implications for nuclear protein quality control. We show that HAPSTR1 is tightly regulated and identify ubiquitin ligase TRIP12 and deubiquitinase USP7 as upstream regulators titrating HAPSTR1 stability. Finally, we generate conditional Hapstr1 knockout mice, finding that Hapstr1-null mice are perinatal lethal, adult mice depleted of Hapstr1 have reduced fitness, and primary cells explanted from Hapstr1-null animals falter in culture coincident with HUWE1 misloc"],"journal":["Life science alliance"],"pubmed_title":["Tight regulation of a nuclear HAPSTR1-HUWE1 pathway essential for mammalian life."],"pmcid":["PMC10921065"],"funding_grant_id":["S10 OD032464","R01 AG078796","T32 CA070085","R01GM144617-01","T32GM008152","R01AG078796","F30CA264513","T32 GM008152","R01 GM144617","P30 CA060553","P30CA060553","RSG-22-086-01-TBE","F30 CA264513"],"pubmed_authors":["King MA","Alasady MJ","Klein AT","Amici DR","Alhayek S","Thakkar A","Wilen AP","Savas JN","Zhu P","Steffeck AW","Mendillo ML","Peek C","Song W","Wang YZ"],"additional_accession":[]},"is_claimable":false,"name":"Tight regulation of a nuclear HAPSTR1-HUWE1 pathway essential for mammalian life.","description":"The recently discovered HAPSTR1 protein broadly oversees cellular stress responses. This function requires HUWE1, a ubiquitin ligase that paradoxically marks HAPSTR1 for degradation, but much about this pathway remains unclear. Here, leveraging multiplexed proteomics, we find that HAPSTR1 enables nuclear localization of HUWE1 with implications for nuclear protein quality control. We show that HAPSTR1 is tightly regulated and identify ubiquitin ligase TRIP12 and deubiquitinase USP7 as upstream regulators titrating HAPSTR1 stability. Finally, we generate conditional Hapstr1 knockout mice, finding that Hapstr1-null mice are perinatal lethal, adult mice depleted of Hapstr1 have reduced fitness, and primary cells explanted from Hapstr1-null animals falter in culture coincident with HUWE1 misloc","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-07-15T00:46:13.014Z","creation":"2026-06-27T03:04:46.191Z"},"accession":"S-EPMC10921065","cross_references":{"pubmed":["38453366"],"doi":["10.26508/lsa.202302370"]}}