Cereblon–Golgi membrane protein 1 complex (CRBN–GOLM1)

The Cereblon–Golgi membrane protein 1 (CRBN–GOLM1) complex is a therapeutic neo-substrate assembly induced by molecular glue degraders. GOLM1, also known as GP73, is a Golgi-resident type II transmembrane protein that is frequently upregulated in solid tumors, most notably hepatocellular carcinoma (HCC), where it drives epithelial-mesenchymal transition, cell proliferation, and metastasis. While GOLM1 is not a natural substrate of the CRL4-CRBN E3 ubiquitin ligase, small molecules like CC-885 act as molecular glues to bridge the interaction between the substrate receptor Cereblon and GOLM1. This induced proximity facilitates the polyubiquitination of GOLM1, leading to its rapid degradation via the 26S proteasome pathway. By depleting GOLM1, these degraders effectively suppress oncogenic signaling and tumor growth in preclinical models. However, the clinical application of such glues faces challenges due to potential off-target degradation of other proteins like GSPT1, which can lead to systemic toxicity.

Other names

CRBN-GP73 complexCereblon-GOLPH2 complexCRBN-GOLM1 complexCereblon-Golgi phosphoprotein 73 complex

Molecular glue-induced targeted protein degradation