Using proteomics to identify ubiquitin ligase–substrate pairs: how novel methods may unveil therapeutic targets for neurodegenerative diseases

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Abstract

Ubiquitin ligases play an integral role in fine-tuning signaling cascades necessary for normal cell function. Aberrant regulation of ubiquitin ligases has been implicated in several neurodegenerative diseases, generally, due to mutations within the E3 ligase itself. Several proteomic-based methods have recently emerged to facilitate the rapid identification of ligase–substrate pairs—a previously challenging feat due to the transient nature of ligase–substrate interactions. These novel methods complement standard immunoprecipitations (IPs) and include proximity-dependent biotin identification (BioID), ubiquitin ligase–substrate trapping, tandem ubiquitin-binding entities (TUBEs), and a molecular trapping unit known as the NEDDylator. The implementation of these techniques is expected to facilitate the rapid identification of novel substrates of E3 ubiquitin ligases, a process that is likely to enhance our understanding of neurodegenerative diseases and highlight novel therapeutic targets for the treatment of neurodegenerative diseases.

LanguageEnglish
Pages2499–2510
Number of pages12
JournalCellular and Molecular Life Sciences
Volume76
Issue number13
Early online date27 Mar 2019
DOIs
Publication statusPublished - Jul 2019

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Ligases
Ubiquitin
Neurodegenerative Diseases
Proteomics
Ubiquitin-Protein Ligases
Therapeutics
Biotin
Immunoprecipitation
Mutation

Keywords

  • BioID
  • E3 ubiquitin ligases
  • Immunoprecipitation
  • Ligase trapping
  • NEDDylator
  • Proteomics
  • TUBE
  • Ubiquitylation

Cite this

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title = "Using proteomics to identify ubiquitin ligase–substrate pairs: how novel methods may unveil therapeutic targets for neurodegenerative diseases",
abstract = "Ubiquitin ligases play an integral role in fine-tuning signaling cascades necessary for normal cell function. Aberrant regulation of ubiquitin ligases has been implicated in several neurodegenerative diseases, generally, due to mutations within the E3 ligase itself. Several proteomic-based methods have recently emerged to facilitate the rapid identification of ligase–substrate pairs—a previously challenging feat due to the transient nature of ligase–substrate interactions. These novel methods complement standard immunoprecipitations (IPs) and include proximity-dependent biotin identification (BioID), ubiquitin ligase–substrate trapping, tandem ubiquitin-binding entities (TUBEs), and a molecular trapping unit known as the NEDDylator. The implementation of these techniques is expected to facilitate the rapid identification of novel substrates of E3 ubiquitin ligases, a process that is likely to enhance our understanding of neurodegenerative diseases and highlight novel therapeutic targets for the treatment of neurodegenerative diseases.",
keywords = "BioID, E3 ubiquitin ligases, Immunoprecipitation, Ligase trapping, NEDDylator, Proteomics, TUBE, Ubiquitylation",
author = "Rayner, {Stephanie L.} and Marco Morsch and Molloy, {Mark P.} and Bingyang Shi and Roger Chung and Albert Lee",
year = "2019",
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language = "English",
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TY - JOUR

T1 - Using proteomics to identify ubiquitin ligase–substrate pairs

T2 - Cellular and Molecular Life Sciences

AU - Rayner, Stephanie L.

AU - Morsch, Marco

AU - Molloy, Mark P.

AU - Shi, Bingyang

AU - Chung, Roger

AU - Lee, Albert

PY - 2019/7

Y1 - 2019/7

N2 - Ubiquitin ligases play an integral role in fine-tuning signaling cascades necessary for normal cell function. Aberrant regulation of ubiquitin ligases has been implicated in several neurodegenerative diseases, generally, due to mutations within the E3 ligase itself. Several proteomic-based methods have recently emerged to facilitate the rapid identification of ligase–substrate pairs—a previously challenging feat due to the transient nature of ligase–substrate interactions. These novel methods complement standard immunoprecipitations (IPs) and include proximity-dependent biotin identification (BioID), ubiquitin ligase–substrate trapping, tandem ubiquitin-binding entities (TUBEs), and a molecular trapping unit known as the NEDDylator. The implementation of these techniques is expected to facilitate the rapid identification of novel substrates of E3 ubiquitin ligases, a process that is likely to enhance our understanding of neurodegenerative diseases and highlight novel therapeutic targets for the treatment of neurodegenerative diseases.

AB - Ubiquitin ligases play an integral role in fine-tuning signaling cascades necessary for normal cell function. Aberrant regulation of ubiquitin ligases has been implicated in several neurodegenerative diseases, generally, due to mutations within the E3 ligase itself. Several proteomic-based methods have recently emerged to facilitate the rapid identification of ligase–substrate pairs—a previously challenging feat due to the transient nature of ligase–substrate interactions. These novel methods complement standard immunoprecipitations (IPs) and include proximity-dependent biotin identification (BioID), ubiquitin ligase–substrate trapping, tandem ubiquitin-binding entities (TUBEs), and a molecular trapping unit known as the NEDDylator. The implementation of these techniques is expected to facilitate the rapid identification of novel substrates of E3 ubiquitin ligases, a process that is likely to enhance our understanding of neurodegenerative diseases and highlight novel therapeutic targets for the treatment of neurodegenerative diseases.

KW - BioID

KW - E3 ubiquitin ligases

KW - Immunoprecipitation

KW - Ligase trapping

KW - NEDDylator

KW - Proteomics

KW - TUBE

KW - Ubiquitylation

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UR - http://purl.org/au-research/grants/nhmrc/1095215

UR - http://purl.org/au-research/grants/nhmrc/1107644

U2 - 10.1007/s00018-019-03082-9

DO - 10.1007/s00018-019-03082-9

M3 - Review article

VL - 76

SP - 2499

EP - 2510

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

SN - 1420-682X

IS - 13

ER -