CRBN: A key E3 ligase receptor for targeted protein degradation.

• Gene Information: CRBN (Cereblon) is encoded on human chromosome 3 and functions as a substrate receptor within the CRL4 E3 ubiquitin ligase complex. It plays a central role in targeted protein degradation.
• Protein Expression: CRBN is broadly expressed across multiple tissues, including immune cells, hematopoietic tissues, and the central nervous system. Its expression level can influence cellular sensitivity to CRBN-recruiting degraders.
• Signaling Pathway: As part of the CRL4^CRBN complex, CRBN recruits substrate proteins for ubiquitination and proteasomal degradation. Binding of IMiDs or molecular glues can redirect CRBN to degrade neosubstrates such as IKZF1, IKZF3, and GSPT1.
• Model application : CRBN is a key target for IMiDs, molecular glues, and PROTACs that induce selective degradation of disease-associated proteins. CRBN-based degraders are being developed for cancer, autoimmune, and inflammatory diseases.

CRBN

• The CDS of human CRBN gene that encodes the full-length protein was inserted into the mouse Crbn exons 2-3. The B-hCRBN mice(C) will express the human CRBN protein, while mouse Crbn will no longer be expressed.

• Mouse Crbn mRNA was detectable in wild-type BALB/cCrSlcNifdc mice. Human CRBN mRNA was detectable only in homozygous B-hCRBN mice(C) but not in wild-type mice.

Strain specific analysis of CRBN mRNA expression in wild-type BALB/cCrSlcNifdc mice and homozygous B-hCRBN mice(C) by RT-PCR. Liver RNA was isolated from wild-type BALB/cCrSlcNifdc mice (+/+) and homozygous B-hCRBN mice(C) (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human CRBN primers. Sequencing of the short-form PCR products confirmed that the amplified sequences were consistent with database reference sequences.

• CRBN protein was detected in the heart, liver, spleen, lung, kidney, small intestine, colon and testis of wild-type BALB/cCrSlcNifdc and homozygous B-hCRBN mice(C).The anti-CRBN antibody was cross-reactive between human and mouse.

Strain specific CRBN expression analysis in homozygous B-hCRBN mice(C) by Western blot. The heart, liver, spleen, lung, kidney, small intestine, colon and testis were collected from wild-type BALB/cCrSlcNifdc mice (+/+) and homozygous B-hCRBN mice(C) (H/H) and then analyzed by western blot with anti-CRBN antibody (CST, #71810).