CRBN
Description
The CRBN (cereblon) is a protein-coding gene located on chromosome 3.
Cereblon is a protein encoded by the CRBN gene in humans. The gene resides on chromosome 3, specifically on the short arm at position p26.3, spanning from base pair 3,190,676 to base pair 3,221,394. CRBN genes are highly conserved across various species, from plants to humans. Cereblon forms a complex with damaged DNA binding protein 1 (DDB1), Cullin-4A (CUL4A), and regulator of cullins 1 (ROC1) to function as an E3 ubiquitin ligase. This complex ubiquitinates various proteins, marking them for degradation through the proteasome. This ubiquitination process leads to reduced levels of fibroblast growth factor 8 (FGF8) and fibroblast growth factor 10 (FGF10), which are crucial for various developmental processes, including limb and auditory vesicle formation. Consequently, this ubiquitin ligase complex is essential for limb outgrowth in embryos. When cereblon is absent, DDB1 forms a complex with DDB2, which functions as a DNA damage-binding protein. Notably, cereblon and DDB2 compete for binding to DDB1.
The CRBN gene encodes a protein called cereblon, which acts as a substrate recognition component in a protein complex called DDB1-CUL4-X-box (DCX) E3 ubiquitin ligase. This complex is responsible for targeting specific proteins for ubiquitination, which marks them for degradation by the proteasome. Cereblon plays a crucial role in several biological processes, including limb development, cognitive function, and immune signaling. In limb development, cereblon is essential for normal outgrowth and expression of the fibroblast growth factor FGF8. It achieves this by ubiquitinating and degrading key regulatory proteins. In the nervous system, cereblon regulates presynaptic glutamate release and cognitive functions, such as memory and learning, by negatively regulating large-conductance calcium-activated potassium (BK) channels in excitatory neurons. This regulation is likely achieved by influencing the assembly and neuronal surface expression of BK channels through its interaction with KCNT1. Cereblon may also contribute to the regulation of anxiety-like behaviors via a BK channel-independent mechanism. In the immune system, cereblon plays a negative role in TLR4 signaling by interacting with TRAF6 and ECSIT, ultimately inhibiting ECSIT ubiquitination, a critical step in the signaling pathway.
CRBN is also known as MRT2, MRT2A.
