Copper transport protein ATOX1 (ATOX1) (ATOX1)

Copper transport protein ATOX1 (ATOX1) is a cytosolic metallochaperone essential for maintaining cellular copper homeostasis by shuttling copper ions to the P-type ATPases ATP7A and ATP7B in the trans-Golgi network [1, 4]. This trafficking process is critical for the maturation of copper-dependent enzymes involved in neovascularization, neurotransmitter synthesis, and collagen formation [3, 7]. Beyond its role as a transporter, ATOX1 functions as a copper-dependent transcription factor and an antioxidant, protecting cells from reactive oxygen species and regulating genes such as cyclin D1 and SOD3 [5, 10]. In oncology, ATOX1 is frequently overexpressed and promotes tumor proliferation, migration, and metastasis, particularly in breast, lung, and hepatocellular cancers [8, 11, 13]. It also interacts with platinum-based chemotherapeutics like cisplatin, potentially mediating drug resistance by sequestering the drug or altering its intracellular trafficking [2, 6]. Therapeutic strategies targeting ATOX1 include small-molecule inhibitors like DCAC50, which disrupt its copper-binding capacity, and copper-sequestering agents like tetrathiomolybdate, which aim to inhibit pro-tumorigenic copper signaling pathways [3, 9].

Other names

HAH1ATX1Antioxidant 1Antioxidant protein 1Copper chaperone ATOX1Human ATX1 homolog

Inhibition of copper transfer to ATP7A/B, copper sequestration, and modulation of copper-dependent transcriptional activity [3, 4, 5].