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Mammalian Expression | … Plasmids expressing human Flag-tagged CRBN (NP_001166953.1) and HA-tagged human CK1α (NP_001883.4) were synthesized in pcDNA3.1 (Addgene) and point mutations introduced by Genscript. Smart-pool siRNA targeting specific genes (AXIN1, APC, and CRBN) … | Get A Quote |
Immunomodulatory drugs (IMiDs) are important for the treatment of multiple myeloma and myelodysplastic syndrome. Binding of IMiDs to Cereblon (CRBN), the substrate receptor of the CRL4 E3 ubiquitin ligase, induces cancer cell death by targeting key neo-substrates for degradation. Despite this clinical significance, the physiological regulation of CRBN remains largely unknown. Herein we demonstrate that Wnt, the extracellular ligand of an essential signal transduction pathway, promotes the CRBN-dependent degradation of a subset of proteins. These substrates include Casein kinase 1α (CK1α), a negative regulator of Wnt signaling that functions as a key component of the β-Catenin destruction complex. Wnt stimula... More