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Updated: May 21, 2026

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
11:36

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

The Roles of VHL-Dependent Ubiquitination in Signaling and Cancer

Qing Zhang1, Haifeng Yang

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School Boston, MA, USA.

Frontiers in Oncology
|June 1, 2012
PubMed

Insights

The VHL tumor suppressor

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The VHL tumor suppressor gene is frequently inactivated in clear cell renal cell carcinoma (ccRCC).
  • The VHL protein (pVHL) functions as part of an E3 ubiquitin ligase complex, targeting specific substrates for degradation.
  • Mutations in VHL often impair its ability to bind and ubiquitinate its targets, particularly Hypoxia-Inducible Factor alpha (HIFα).

Purpose of the Study:

  • To review the known functions of the VHL tumor suppressor.
  • To discuss the role of pVHL in targeting various substrates beyond HIFα.
  • To explore the implications of pVHL substrate regulation in cancer signaling and drug response.

Main Methods:

  • Literature review and synthesis of existing research on VHL function and substrates.
  • Analysis of the biochemical mechanisms underlying pVHL-substrate interactions.
  • Discussion of the oncogenic potential of dysregulated pVHL targets.

Main Results:

  • pVHL targets HIFα for ubiquitination and degradation, a key mechanism in its tumor suppressor activity.
  • pVHL also targets other proteins, including activated epidermal growth factor receptor (EGFR) and protein kinase C (PKC).
  • Dysregulation of these additional pVHL substrates may contribute to tumor growth and affect drug sensitivity.

Conclusions:

  • pVHL's tumor suppressor function is primarily mediated through HIFα regulation, but other substrates are also critical.
  • Understanding the broader substrate interactions of pVHL offers insights into ccRCC pathogenesis.
  • Targeting pVHL substrates presents potential therapeutic strategies for renal cell carcinoma.
Keywords:
EGFRHIFVHLccRCCproline hydroxylationubiquitin

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