ArticleThe EMBO journal2003
The VHL protein recruits a novel KRAB-A domain protein to repress HIF-1alpha transcriptional activity.
Article in The EMBO journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 77 citations in OpenAlex.
- TRIM28 regulates sprouting angiogenesis through VEGFR-DLL4-Notch signaling circuit.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Copper associates with differential methylation in placentae from two US birth cohorts.Epigenetics · 2020Article
- miRNA Expression Profile in the N2 Phenotype Neutrophils of Colorectal Cancer and Screen of Putative Key miRNAs.Cancer management and research · 2020Article
- TRIM17 and TRIM28 antagonistically regulate the ubiquitination and anti-apoptotic activity of BCL2A1.Cell death and differentiation · 2019Article
- ZBRK1, a novel tumor suppressor, activates VHL gene transcription through formation of a complex with VHL and p300 in renal cancer.Oncotarget · 2015Article
- KAP1 promotes proliferation and metastatic progression of breast cancer cells.Cancer research · 2015Article
- KAPtain in charge of multiple missions: Emerging roles of KAP1.World journal of biological chemistry · 2014Review
- Identification of novel hypoxia response genes in human glioma cell line a172.Iranian journal of basic medical sciences · 2013Article
- Cutting Edge: a novel, human-specific interacting protein couples FOXP3 to a chromatin-remodeling complex that contains KAP1/TRIM28.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- A unique SUMO-2-interacting motif within LANA is essential for KSHV latency.PLoS pathogens · 2013Article
- KAP1 protein: an enigmatic master regulator of the genome.The Journal of biological chemistry · 2011Review
- Hypoxic repression of endothelial nitric-oxide synthase transcription is coupled with eviction of promoter histones.The Journal of biological chemistry · 2010Article
- Epigenetic gene silencing by the SRY protein is mediated by a KRAB-O protein that recruits the KAP1 co-repressor machinery.The Journal of biological chemistry · 2009Article
- The VHL tumor suppressor: master regulator of HIF.Current pharmaceutical design · 2009Review
- Germline mutations in the von Hippel-Lindau disease (VHL) gene in mainland Chinese families.Journal of cancer research and clinical oncology · 2008Article
- The VHL tumor suppressor and HIF: insights from genetic studies in mice.Cell death and differentiation · 2008Review
- Central nervous system capillary haemangioblastoma: the pathologist's viewpoint.International journal of experimental pathology · 2007Review
- The transcriptional repressor K-RBP modulates RTA-mediated transactivation and lytic replication of Kaposi's sarcoma-associated herpesvirus.Journal of virology · 2007Article
- Current understanding of the molecular mechanisms of kidney cancer: a primer for urologists.Canadian Urological Association journal = Journal de l'Association des urologues du Canada · 2007Article
- A yeast two-hybrid system reconstituting substrate recognition of the von Hippel-Lindau tumor suppressor protein.Nucleic acids research · 2007Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The von Hippel-Lindau tumor suppressor (pVHL) is a component of an E3 ubiquitin ligase and targets hypoxia-inducible factor-1alpha (HIF-1alpha) for ubiquitylation and degradation under normoxic conditions. pVHL also directly inhibits HIF-1alpha transactivation by recruiting histone deacetylases. Here, we report a novel pVHL-interacting protein that functions as a negative regulator of HIF-1alpha transactivation. This protein, generated from the ZnF197 locus by alternative splicing, contains a Kruppel-associated box (KRAB)-A domain and a SCAN domain, but lacks the 22 C2H2-type zinc fingers present in ZnF197. Therefore, we named this protein pVHL-associated KRAB-A domain-containing protein (VHLaK). We demonstrate that the KRAB-A domain in VHLaK mediates pVHL binding and functions as a transcriptional repression module. The SCAN domain mediates VHLaK homo-oligomerization, which enhances VHLaK repressive activity. pVHL can recruit VHLaK to repress HIF-1alpha transcriptional activity and HIF-1alpha-induced VEGF expression. Finally, we demonstrate that pVHL, VHLaK and KAP1/TIF-1beta can be recruited into a single complex, indicating that KAP1/TIF-1beta may participate in pVHL-mediated transcriptional repression of HIF-1alpha. Our findings provide a novel mechanism for the modulation of HIF-1alpha transactivation by pVHL.
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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.