Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

NAD(P)H oxidases regulate HIF-2alpha protein expression.

Karen Block1, Yves Gorin, Paul Hoover

  • 1Division of Nephrology, Department of Medicine, George O'Brien Kidney Research Center, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA. block@uthscsa.edu

The Journal of Biological Chemistry
|January 4, 2007
PubMed
Summary

The von Hippel-Lindau (VHL) tumor suppressor protein inhibits reactive oxygen species (ROS) production by blocking p22phox-based NADPH oxidases. This mechanism is crucial for VHL

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Smoking inequalities among culturally diverse populations in Australia: A secondary dataset analysis of the HILDA survey 2002-2019.

Tobacco induced diseases·2026
Same author

Beyond initial care: a mixed-methods study of hospital-based health services for women and girls who have experienced sexual violence in Ethiopia.

BMJ open·2026
Same author

Spatially Distinct Macrophage Subsets Drive Myofibroblast Heterogeneity and Maladaptive Fibrosis in Lupus Nephritis.

bioRxiv : the preprint server for biology·2026
Same author

Hospital-based services for survivors of sexual violence in Ethiopia: who is missing out? A mixed-methods study.

BMJ global health·2026
Same author

Unmet need for health care services among Rohingya Refugees living in Cox's Bazar and Bhasan Char in Bangladesh.

PLOS global public health·2026
Same author

Prevalence and factors associated with psychosocial distress and trauma among Rohingya refugees living in Cox's Bazar and Bhasan Char in Bangladesh.

Journal of migration and health·2025

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Biallelic inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene is implicated in renal cell carcinoma (RCC) development.
  • VHL deficiency leads to stabilization of hypoxia-inducible transcription factors (HIFs).
  • Reactive oxygen species (ROS), generated by NAD(P)H oxidases, are involved in cancer signaling pathways.

Purpose of the Study:

  • To investigate the role of VHL in regulating ROS production and its impact on HIF stabilization in VHL-deficient cells.
  • To determine if p22phox and NADPH oxidases are targets of VHL's tumor suppressor activity.

Main Methods:

  • Analysis of p22phox, Nox4 protein levels, and NADPH-dependent superoxide generation in VHL-deficient and VHL-reconstituted cells.
  • Co-immunoprecipitation and ubiquitination assays to study VHL-p22phox interaction.

Related Experiment Videos

  • Inhibition of Nox oxidases using diphenyleneiodonium chloride (DPI) and gene silencing (siRNA) to assess effects on HIF-2alpha, Akt, and 4E-BP1.
  • In vitro and in vivo tumor formation assays using RCC 786-O cells.

    • Main Results:

    • VHL-deficient cells exhibit increased p22phox, Nox4, and NADPH-dependent superoxide generation.
    • Reintroduction of VHL down-regulates p22phox and ROS production.
    • p22phox interacts with VHL and is a target of ubiquitination.
    • Nox oxidase inhibition (DPI) reduces HIF-2alpha levels and downstream signaling, and inhibits RCC cell proliferation and tumor growth.

    Conclusions:

    • The VHL tumor suppressor protein inhibits ROS generation by suppressing p22phox-based Nox4/Nox1 NADPH oxidase activity.
    • This VHL-mediated inhibition of ROS is a key mechanism contributing to its tumor suppressor function in renal cell carcinoma.
    • Targeting Nox oxidases may represent a therapeutic strategy for VHL-deficient RCC.