ArticleProceedings of the National Academy of Sciences of the United States of America2013
BC-box protein domain-related mechanism for VHL protein degradation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Von Hippel-Lindau/Hypoxia Inducible Factor Axis in Glioblastoma.International journal of molecular sciences · 2025Review
- SOCS domain targets ECM assembly in lung fibroblasts and experimental lung fibrosis.Scientific reports · 2024Article
- REST-dependent downregulation of von Hippel-Lindau tumor suppressor promotes autophagy in SHH-medulloblastoma.Scientific reports · 2024Article
- Clinical implications of activation of the LIMD1-VHL-HIF1α pathway during head-&-neck squamous cell carcinoma development.The Indian journal of medical research · 2024Article
- SOCS domain targets ECM assembly in lung fibroblasts and experimental lung fibrosis.bioRxiv : the preprint server for biology · 2024Article
- Lysine deserts and cullin-RING ligase receptors: Navigating untrodden paths in proteostasis.iScience · 2023Article
- c-MYC-dependent transcriptional inhibition of autophagy is implicated in cisplatin sensitivity in HPV-positive head and neck cancer.Cell death & disease · 2023Article
- HPV-mediated regulation of SMAD4 modulates the DNA damage response in head and neck cancer.Journal of experimental & clinical cancer research : CR · 2022Article
- Enhanced glucose metabolism through activation of HIF-1α covers the energy demand in a rat embryonic heart primordium after heartbeat initiation.Scientific reports · 2022Article
- Article
- Human Papilloma Virus Increases ΔNp63α Expression in Head and Neck Squamous Cell Carcinoma.Frontiers in cellular and infection microbiology · 2020Article
- CRL4The EMBO journal · 2018Article
- Autophagy regulates UBC9 levels during viral-mediated tumorigenesis.PLoS pathogens · 2017Article
- WSB1 overcomes oncogene-induced senescence by targeting ATM for degradation.Cell research · 2017Article
- Newcastle disease virus degrades HIF-1α through proteasomal pathways independent of VHL and p53.The Journal of general virology · 2016Article
- USP9X destabilizes pVHL and promotes cell proliferation.Oncotarget · 2016Article
- WSB1 promotes tumor metastasis by inducing pVHL degradation.Genes & development · 2015Article
- VHL negatively regulates SARS coronavirus replication by modulating nsp16 ubiquitination and stability.Biochemical and biophysical research communications · 2015Article
- Expression and in vitro functional analyses of recombinant Gam1 protein.Protein expression and purification · 2015Article
- The SUMO conjugating enzyme UBC9 as a biomarker for cervical HPV infections.Ecancermedicalscience · 2015Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 4 countries.
Funding
Abstract
The tumor suppressor VHL (von Hippel-Lindau) protein is a substrate receptor for Ubiquitin Cullin Ring Ligase complexes (CRLs), containing a BC-box domain that associates to the adaptor Elongin B/C. VHL targets hypoxia-inducible factor 1α to proteasome-dependent degradation. Gam1 is an adenoviral protein, which also possesses a BC-box domain that interacts with the host Elongin B/C, thereby acting as a viral substrate receptor. Gam1 associates with both Cullin2 and Cullin5 to form CRL complexes targeting the host protein SUMO enzyme SAE1 for proteasomal degradation. We show that Gam1 protein expression induces VHL protein degradation leading to hypoxia-inducible factor 1α stabilization and induction of its downstream targets. We also characterize the CRL-dependent mechanism that drives VHL protein degradation via proteasome. Interestingly, expression of Suppressor of Cytokine Signaling (SOCS) domain-containing viral proteins and cellular BC-box proteins leads to VHL protein degradation, in a SOCS domain-containing manner. Our work underscores the exquisite ability of viral domains to uncover new regulatory mechanisms by hijacking key cellular proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.