PDZ domain-containing protein GIPC1 (GIPC1)

PDZ domain-containing protein GIPC1, also known as GAIP-interacting protein C terminus 1, is a critical scaffolding protein that regulates the trafficking and signaling of numerous transmembrane receptors. It features a central PDZ domain that facilitates binding to the C-terminal motifs of various cargo proteins, including Insulin-like Growth Factor 1 Receptor (IGF-1R), Neuropilin-1 (NRP1), and Glucose Transporter 1 (GLUT1). By modulating the endocytosis and recycling of these molecules, GIPC1 ensures proper cellular signaling and metabolic homeostasis. In the context of oncology, GIPC1 is frequently overexpressed in aggressive malignancies such as pancreatic and breast cancers, where it stabilizes growth factor receptors to promote tumor cell proliferation, survival, and invasion. Therapeutic development is currently focused on small molecule inhibitors and cell-penetrating peptides designed to block the GIPC1 PDZ domain, thereby disrupting oncogenic protein complexes and inducing the degradation of target receptors. While these inhibitors are primarily in the preclinical stage, GIPC1 represents a promising target for disrupting the scaffolding networks that drive cancer progression.

Other names

GAIP-interacting protein C terminus 1RGS19-interacting protein 1GLUT1 C-terminal-binding proteinSemaphorin-cytoplasmic domain-associated protein 1SEMCAP-1Tax-interacting protein 2TIP-2IIP-1GIPC

Inhibition of the GIPC1 PDZ domain to disrupt protein-protein interactions with oncogenic receptors, leading to receptor degradation and impaired downstream signaling.