Identifying E3 ligase substrates with quantitative degradation proteomics Journal Article

   


Authors: Jordan, V. N.; Ordureau, A.; An, H.
Article Title: Identifying E3 ligase substrates with quantitative degradation proteomics
Abstract: Controlled protein degradation by the ubiquitin-proteasome pathway is critical for almost all cellular processes. E3 ubiquitin ligases are responsible for targeting proteins for ubiquitylation and subsequent proteasomal degradation with spatial and temporal precision. While studies have revealed various E3-substrate pairs involved in distinct biological processes, the complete substrate profiles of individual E3 ligases are largely unknown. Here we report a new approach to identify substrates of an E3 ligase for proteasomal degradation using unnatural amino acid incorporation pulse-chase proteomics (degradomics). Applying this approach, we determine the steady-state substrates of the C-terminal to LisH (CTLH) E3 ligase, a multi-component complex with poorly defined substrates. By comparing the proteome degradation profiles of active and inactive CTLH-expressing cells, we successfully identify previously known and new potential substrates of CTLH ligase. Altogether, degradomics can comprehensively identify degradation substrates of an E3 ligase, which can be adapted for other E3 ligases in various cellular contexts. © 2023 Wiley-VCH Verlag GmbH.
Keywords: ubiquitin; metabolism; ubiquitin protein ligase; protein degradation; proteomics; ubiquitination; ubiquitin-protein ligases; ubiquitins; proteolysis; ctlh; degradomics; protein half-life; the ubiquitin proteasome system
Journal Title: ChemBioChem
Volume: 24
Issue: 16
ISSN: 1439-4227
Publisher: Wiley V C H Verlag Gmbh  
Date Published: 2023-08-15
Start Page: e202300108
Language: English
DOI: 10.1002/cbic.202300108
PUBMED: 37166757
PROVIDER: scopus
PMCID: PMC10548883
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85165211718&doi=10.1002%2fcbic.202300108&partnerID=40&md5=08a227246fd9369b57cf448b470137fd
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in PubMed and PDF -- Corresponding author is MSK author: Heeseon An -- Source: Scopus
Altmetric
What is Altmetric?
Citation Impact
What is Dimensions Citation Badge?
BMJ Impact Analytics
MSK Authors
  1. Alban Simon Georges Ordureau
    16 Ordureau
  2. Victoria N Jordan
    1 Jordan
  3. Heeseon An
    4 An
Related MSK Work