Molecular Classification
E3 Ubiquitin Ligase Complex, Enzyme Complex
Other Names
Cereblon complex
Disease Roles
Multiple myelomaIntellectual disability syndromesNeurodevelopmental disorders

Cereblon E3 Ubiquitin Ligase Complex Overview

The Cereblon E3 ubiquitin ligase complex is a multi-protein assembly that plays a central role in targeted protein degradation within cells. It is best known for its involvement in the ubiquitin-proteasome pathway, where it tags specific proteins with ubiquitin molecules, marking them for destruction by the proteasome. The core components include Cereblon (CRBN), DDB1, CUL4A/B, and ROC1/RBX1. CRBN acts as the substrate receptor, determining which proteins are selected for ubiquitination. This complex regulates diverse cellular processes and is targeted by drugs like thalidomide and its analogs, altering its substrate specificity. It is also an attractive component in PROTACs for targeted protein degradation therapies.

Mechanism of Action

Modulation of substrate specificity leading to targeted protein degradation

Biological Functions

Selective polyubiquitination
Protein degradation
Signal transduction
Cell cycle progression
DNA damage response
Embryonic development
Regulation of gene expression

Disease Associations

Multiple myeloma
Intellectual disability syndromes
Neurodevelopmental disorders

Safety Considerations

  • Teratogenicity (thalidomide)
  • Potential for off-target effects due to altered substrate specificity

Interacting Drugs

Thalidomide
Lenalidomide
Pomalidomide