Adipocyte enhancer-binding protein 1–Cytoskeleton-associated protein 4 protein–protein interface (AEBP1–CKAP4 interface)

The AEBP1–CKAP4 protein–protein interface is a critical signaling complex formed by the binding of secreted Adipocyte Enhancer-Binding Protein 1 (AEBP1), also known as Adipocyte-derived Leucine-rich Protein (ACLP), to the extracellular domain of Cytoskeleton-Associated Protein 4 (CKAP4) (UniProt Q8IUX7, Q07065). AEBP1 is a multi-domain protein associated with the extracellular matrix that regulates collagen fiber assembly and TGF-beta signaling. The interaction between AEBP1 and CKAP4 functions as a potent trigger for intracellular signaling pathways, including PI3K/AKT and MAPK/ERK, which are essential for cell survival, proliferation, and migration (PubMed: 31601211). In clinical contexts, this interface is highly relevant to oncology, particularly in glioblastoma and gastric cancer, where it promotes an aggressive, invasive phenotype and epithelial-mesenchymal transition (EMT) (PubMed: 33050916). Additionally, the AEBP1–CKAP4 axis plays a significant role in pathological fibrosis and vascular remodeling by driving myofibroblast activation. Therapeutic intervention strategies focus on developing monoclonal antibodies or small-molecule inhibitors that can sterically hinder this interface, thereby neutralizing the pro-tumorigenic and pro-fibrotic signals initiated by AEBP1.

Other names

ACLP–CKAP4 interactionAEBP1–CLIMP-63 complexAdipocyte-derived leucine-rich protein–CKAP4 interfaceAEBP1–CKAP4 axis

Inhibition of the protein-protein interaction between secreted AEBP1 and the transmembrane receptor CKAP4 to prevent the activation of downstream oncogenic and profibrotic signaling pathways, such as PI3K/AKT and MAPK/ERK.