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Cul5: immune cell function and therapeutic potential.

Siera A Tomishima1, Paula M Oliver1,2

  • 1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.

Frontiers in Immunology
|May 1, 2026
PubMed
Summary
This summary is machine-generated.

Immune cells use E3 ubiquitin ligases (E3s) to control signaling pathways and maintain homeostasis. This review highlights Cullin Ring Ligase 5 (CRL5) complexes in regulating immune cell function and potential therapeutic targets.

Keywords:
E3 ubiqitin ligaseSOCS proteinscullin 5immune cellsubiquitin proteasomal system

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Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • Immune cells detect pathogens and danger signals via surface receptors, activating transcriptional programs for defense.
  • Rapid switching between activated states and homeostasis requires precise control of signaling pathways.
  • Post-transcriptional regulation, including by E3 ubiquitin ligases (E3s), is crucial for modulating immune cell behavior.

Purpose of the Study:

  • To provide an overview of the ubiquitin proteasome system (UPS).
  • To review new insights into how Cullin 5 (Cul5) and Cullin Ring Ligase 5 (CRL5) complexes regulate immune cell function.
  • To discuss therapeutic strategies targeting the UPS and CRL5 for disease treatment.

Main Methods:

  • Literature review of the ubiquitin proteasome system (UPS).
  • Analysis of the role of Cullin 5 (Cul5) and its associated complexes (CRL5).
  • Examination of Suppressors of Cytokine Signaling (SOCS)-box proteins in substrate recruitment.

Main Results:

  • E3 ubiquitin ligases, particularly CRL5 complexes, are key regulators of immune cell signaling and function.
  • CRL5, in conjunction with SOCS-box proteins, mediates targeted protein degradation crucial for immune responses.
  • Understanding CRL5 regulation offers insights into immune cell proliferation, differentiation, and homeostasis.

Conclusions:

  • CRL5 complexes play a vital role in regulating immune cell function through targeted protein degradation.
  • The UPS, and specifically CRL5, represents a promising area for therapeutic intervention in various diseases.
  • Targeting CRL5 offers potential for developing novel treatments for immune-related disorders.