Related Experiment Video

Updated: Mar 15, 2026

Functional Characterization of RING-Type E3 Ubiquitin Ligases In Vitro and In Planta
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Functional Characterization of RING-Type E3 Ubiquitin Ligases In Vitro and In Planta

Published on: December 5, 2019

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Cullin-RING receptors in rare disease biology

Natalia A Szulc1, Wojciech Pokrzywa1

  • 1Laboratory of Protein Metabolism, International Institute of Molecular and Cell Biology in Warsaw, 4 Ks. Trojdena Street, Warsaw 02-109, Poland.

Trends in Cell Biology
|March 13, 2026
PubMed

Insights

Substrate receptors (SRs) are key to protein degradation and human genetic diseases. This review catalogs 267 SRs, linking 93 to disorders and highlighting their therapeutic potential in precision medicine.

Area of Science:

  • Biochemistry and Molecular Biology
  • Genetics and Genomics
  • Cell Biology

Background:

  • The ubiquitin-proteasome system (UPS) regulates protein turnover, crucial for cellular function.
  • Cullin-RING (CRL) E3 ligases are the largest family of E3 ligases within the UPS.
  • Substrate receptors (SRs) confer substrate specificity to CRLs, acting as 'specificity engines'.

Purpose of the Study:

  • To systematically catalogue known substrate receptors (SRs).
  • To identify SRs linked to human germline disorders.
  • To synthesize current understanding of SR mechanisms and their role in disease.

Main Methods:

  • Comprehensive literature review and database analysis.
  • Systematic cataloging of 267 identified SRs.
  • Analysis of genetic variant data associated with human disorders.

Main Results:

  • A catalogue of 267 SRs was compiled.
  • 93 SRs are currently linked to human germline disorders.
  • Emerging mechanisms include altered degron recognition and noncanonical SR functions.

Conclusions:

  • SRs are critical mediators of protein degradation with significant implications for human genetic diseases.
  • Patient variants in SRs offer insights into disease pathways, diagnosis, and potential therapies.
  • SRs represent key targets for advancing precision medicine through targeted protein degradation.
Keywords:
E3 ubiquitin ligasescullin–RING ligasesgermline variantsrare genetic diseasessubstrate receptorsubiquitin–proteasome system

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