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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

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Ubiquitylation of nuclear receptors: new linkages and therapeutic implications

Kyle T Helzer1, Christopher Hooper1, Shigeki Miyamoto1

  • 1McArdle Laboratory for Cancer ResearchDepartment of Oncology, 6151 Wisconsin Institutes for Medical Research, University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.

Journal of Molecular Endocrinology
|May 7, 2015
PubMed

Insights

Nuclear receptors (NRs) regulate physiology and disease. This review explores NR ubiquitylation, a process that could reveal new therapeutic targets to overcome drug resistance.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • Nuclear receptors (NRs) are crucial transcriptional regulators involved in numerous physiological and pathological processes.
  • NRs are established therapeutic targets, but drug resistance necessitates the discovery of novel strategies.
  • Targeting NR signaling pathways has yielded successful therapies, yet challenges remain.

Purpose of the Study:

  • To review the role of NR ubiquitylation in regulating NR function.
  • To explore how ubiquitin signaling can be leveraged for new therapeutic development against NRs.
  • To identify novel entry points for controlling NR activity and overcoming therapeutic resistance.

Main Methods:

  • Literature review focusing on NR ubiquitylation and ubiquitin signaling.
  • Analysis of existing research on NR-targeted therapies and resistance mechanisms.
  • Discussion of potential therapeutic strategies based on ubiquitin-mediated NR regulation.

Main Results:

  • Ubiquitylation is a key post-translational modification influencing NR stability, localization, and transcriptional activity.
  • Specific ubiquitylation events can either activate or inhibit NR signaling, offering nuanced control points.
  • The ubiquitin system presents a rich source of potential targets for modulating NR function.

Conclusions:

  • NR ubiquitylation plays a critical role in NR signaling and offers promising avenues for therapeutic intervention.
  • Leveraging ubiquitin pathways could lead to the development of next-generation NR-targeting drugs with improved efficacy.
  • Understanding NR ubiquitylation is essential for overcoming resistance and advancing NR-targeted therapies.
Keywords:
E3 ligaseNF-κBproteasomesteroid

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