ArticleScience (New York, N.Y.)2018
VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma.
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Article in Science (New York, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.
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138citing papers in PubMed
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Who cites it
138 citing papers in PubMed.
- Beyond hypoxia and ccRCC: the expanding universe of VHL novel targets and next-generation therapeutics.Biomarker research · 2026Review
- SPOP-mediated ZMYND8 ubiquitination and phase separation exclusion drives mTOR inhibitor resistance in kidney cancer.Nature communications · 2026Article
- ZHX2 Alleviates Vascular Remodeling and Smooth Muscle Cell Proliferation by Transcriptional Regulation of GADD45G.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Recent advances in etiology and treatment of von Hippel-Lindau Disease (VHLD).Cancer metastasis reviews · 2026Review
- Identification of methylation-sensitive human transcription factors using meSMiLE-seq.Nature communications · 2026Article
- Rescuing the Function of Missense-Mutated Tumor SuppressorbioRxiv : the preprint server for biology · 2026Article
- Genome-wide CRISPR screen identifies a cytokine-enhancer circuit driving HIF-2α activation in renal cancer.The Journal of clinical investigation · 2026Article
- CDK6/4 inactivates BAP1 deubiquitinase destabilizing VHL to promote metastatic colonization in liver.Molecular cancer · 2026Article
- Glucocorticoids elevate clear cell renal cell carcinoma sensitivity to HIF-2α inhibitors by suppressing H4K12 lactylation.Signal transduction and targeted therapy · 2026Article
- DR5/WDR12 balances p65 stability promoting sunitinib resistance in renal cell carcinoma.Cell death and differentiation · 2026Article
- Hypoxia-induced MT2A-tetrameric PKM2 interaction maintains PKM2 activity in a copper-ion-dependent manner.Cell insight · 2025Article
- The SLC1A1/EAAT3 dicarboxylic amino acid transporter is an epigenetically dysregulated nutrient carrier that sustains oncogenic metabolic programs.Nature communications · 2025Article
- D-mannose suppresses HIF-1α mediated metabolic reprogramming in clear cell renal cell carcinoma.Discover oncology · 2025Article
- Liquid-liquid phase separation of ZHX2 protects DLBCL cells against ferroptosis through induction of SLC3A2.Leukemia · 2025Article
- pVHL regulates protein stability of the TCF/LEF transcription factor family via ubiquitin-independent proteasomal degradation.Cellular and molecular life sciences : CMLS · 2025Article
- The Transcription Factor CREB1 Triggers the Progression of Clear Cell Renal Cell Carcinoma by Promoting CENPE Expression.Journal of cellular and molecular medicine · 2025Article
- Programmed Cell Death Protein 10 (PDCD10) Regulates Vesicle Trafficking and Contributes to the Progression of Clear Cell Renal Cell Carcinoma.Journal of extracellular vesicles · 2025Article
- Hypoxia-specific transcriptional condensates drive metastasis.Trends in cell biology · 2025Article
- Synthetic essentiality of TRAIL/TNFSF10 in VHL-deficient renal cell carcinoma.bioRxiv : the preprint server for biology · 2025Article
- MYLIP attenuates hypoxia tolerance by inducing K27-linked polyubiquitination and subsequent proteasomal degradation of HIF-α.Communications biology · 2025Article
78 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors.
Jing ZhangLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.ORCID 0000-0001-6438-9113
Tao WuDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-5380-3905
Jeremy SimonLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.ORCID 0000-0003-3906-1663
Mamoru TakadaLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.ORCID 0000-0002-3961-9009
Ryoichi SaitoLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Cheng FanLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Xian-De LiuDepartments of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-9639-0458
Eric JonaschDepartments of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-0943-2806
Ling XieDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.
Xian ChenDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.
Xiaosai YaoCancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore 138672, Singapore.ORCID 0000-0001-9729-0726
Bin Tean TehInstitute of Molecular and Cell Biology, Singapore 138673, Singapore.ORCID 0000-0003-1514-1124
Patrick TanCancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore 138672, Singapore.
Xingnan ZhengLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.ORCID 0000-0003-3034-4421
Mingjie LiLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.ORCID 0000-0001-5337-4901
Cortney LawrenceLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Jie FanDepartment of Pathology, Huashan Hospital, Fudan University, Shanghai, China.ORCID 0000-0003-3842-2391
Jiang GengDepartment of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.ORCID 0000-0002-7202-2167
Xijuan LiuLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Lianxin HuLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Jun WangLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Chengheng LiaoLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Kai HongLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Giada ZurloLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Joel S ParkerLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.ORCID 0000-0003-2080-6901
J Todd AumanLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.ORCID 0000-0002-9328-8829
Charles M PerouLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.ORCID 0000-0001-9827-2247
W Kimryn RathmellDivision of Hematology and Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.ORCID 0000-0002-4984-0225
William Y KimLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Marc W KirschnerDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-6540-6130
William G KaelinHoward Hughes Medical Institute, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.ORCID 0000-0002-0574-4856
Albert S BaldwinLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.ORCID 0000-0003-1246-1333
Qing ZhangLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. qing_zhang@med.unc.edu.ORCID 0000-0002-6595-8995
Funding
Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5MUNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Melissa A. Troester · 2001 to 2026
$36.3MUNC Neuroscience Center Research Cores: MicroscopyP30NS045892 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ZYLKA, MARK J. · 2003 to 2022
$11.5MThe von Hippel-Lindau Tumor Suppressor Gene and Kidney Cancer: Insights into Oxygen Sensing and Treating Cancers Caused by Undruggable MutationsR35CA210068 · NCI · DANA-FARBER CANCER INST · PI WILLIAM G. KAELIN · 2016 to 2026
$10.8MIKK/NF-kappaB Signaling in Cancer: Therapy, Resistance, and Tumor Initiating CellsR35CA197684 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BALDWIN, ALBERT SIDNEY · 2016 to 2022
$5.8MExploration of ZHX2 as a novel substrate of pVHL and an oncogenic driver of renal cancerR01CA211732 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI ZHANG, QING · 2017 to 2021
$2.1MRole of the EglN2 Target FOXO3a in Breast CancerR00CA160351 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ZHANG, QING · 2013 to 2015
$725kOTUB1 as a Novel Therapeutic Target in Kidney Cancer by Deubiquitinating HIF2alphaR21CA223675 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BALDWIN, ALBERT SIDNEY · 2018 to 2019
$366kNCI NIH HHS P30 CA016086NCI NIH HHS R00 CA160351NCI NIH HHS R01 CA211732NCI NIH HHS R21 CA223675NCI NIH HHS R35 CA197684NCI NIH HHS R35 CA210068NIEHS NIH HHS P30 ES010126NINDS NIH HHS P30 NS045892
Abstract
Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bind VHL when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability. Tumor cells from ccRCC patients with
Indexed as
OncogenesAnimalsCarcinoma, Renal CellChromatin ImmunoprecipitationFemaleGene Expression Regulation, NeoplasticHomeodomain ProteinsHumansHydroxylationKidney NeoplasmsMiceMice, SCIDMolecular Targeted TherapyMutationNF-kappa BSubstrate SpecificityHomeodomain ProteinsNF-kappa BTranscription FactorsVHL protein, humanVon Hippel-Lindau Tumor Suppressor ProteinZHX2 protein, human
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