{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang S"],"funding":["Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)","Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)","National Natural Science Foundation of China (National Science Foundation of China)","Taishan Scholar Foundation of Shandong Province"],"pagination":["446"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11196597"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(6)"],"pubmed_abstract":["Protein homeostasis is predominantly governed through post-translational modification (PTM). UBE3B, identified as an oncoprotein, exhibits elevated protein levels in breast cancer. However, the impact of PTM on UBE3B remains unexplored. In this study, we show that VHL is a bona fide E3 ligase for UBE3B. Mechanistically, VHL directly binds to UBE3B, facilitating its lysine 48 (K48)-linked polyubiquitination at K286 and K427 in a prolyl hydroxylase (PHD)-independent manner. Consequently, this promotes the proteasomal degradation of UBE3B. The K286/427R mutation of UBE3B dramatically abolishes the inhibitory effect of VHL on breast tumor growth and lung metastasis. Additionally, the protein levels of UBE3B and VHL exhibit a negative correlation in breast cancer tissues. These findings delinea"],"journal":["Cell death & disease"],"pubmed_title":["VHL suppresses UBE3B-mediated breast tumor growth and metastasis."],"pmcid":["PMC11196597"],"funding_grant_id":["tsqn202306155","2021A1515011224","2022A1515011738","82203297","ZR2023MH252","81902691","tsqn202306154"],"pubmed_authors":["Liu X","Li H","Yin T","Li T","Liu M","Wang S","Zheng M","Chen Y","Wang Y","Meng X","Zhou J"],"additional_accession":[]},"is_claimable":false,"name":"VHL suppresses UBE3B-mediated breast tumor growth and metastasis.","description":"Protein homeostasis is predominantly governed through post-translational modification (PTM). UBE3B, identified as an oncoprotein, exhibits elevated protein levels in breast cancer. However, the impact of PTM on UBE3B remains unexplored. In this study, we show that VHL is a bona fide E3 ligase for UBE3B. Mechanistically, VHL directly binds to UBE3B, facilitating its lysine 48 (K48)-linked polyubiquitination at K286 and K427 in a prolyl hydroxylase (PHD)-independent manner. Consequently, this promotes the proteasomal degradation of UBE3B. The K286/427R mutation of UBE3B dramatically abolishes the inhibitory effect of VHL on breast tumor growth and lung metastasis. Additionally, the protein levels of UBE3B and VHL exhibit a negative correlation in breast cancer tissues. These findings delinea","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jun","modification":"2025-04-19T08:39:15.482Z","creation":"2025-04-19T08:39:15.482Z"},"accession":"S-EPMC11196597","cross_references":{"pubmed":["38914543"],"doi":["10.1038/s41419-024-06844-x"]}}