(±)-Thalidomide, Immunomodulator and anticancer agent

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

CRBN also known as cereblon is a protein involved in the regulation of protein homeostasis. It has a molecular weight of approximately 51 kDa. CRBN is expressed in various tissues including the brain kidney and muscle. It functions as a substrate receptor for the CRL4-CRBN E3 ubiquitin ligase complex recognizing proteins for ubiquitination and degradation. The chemical structure of thalidomide shows binding affinity to CRBN influencing its function.

Biological function summary

Cereblon plays a role in the regulation of protein stability and degradation. It forms part of the CRL4-CRBN complex which tags specific proteins for ubiquitination and subsequent proteasomal degradation. This function is critical for maintaining cellular protein balance. Additionally CRBN modulates immune response and has immunomodulator properties influencing cell-mediated responses.

Pathways

CRBN participates in the ubiquitin-proteasome pathway which regulates protein turnover and quality control within cells. Moreover CRBN is involved in immune signaling pathways partly by modulating the expression of various cytokines and immune-related proteins. It interacts with proteins such as DDB1 and CUL4 within these pathways impacting cellular responses to stress and immune challenges.

CRBN is associated with multiple myeloma and intellectual disability. Cereblon acts as a target for drugs like thalidomide and lenalidomide which are used in the treatment of multiple myeloma by altering ubiquitination processes. In intellectual disability alterations in CRBN function or expression can disrupt neuronal development and signaling. CRBN interacts with proteins like IKZF1 and IKZF3 within these contexts affecting their roles in disease progression and treatment responses.