Antioxidant 1 copper chaperone (ATOX1) (ATOX1)

Antioxidant 1 copper chaperone (ATOX1) is a small, highly conserved cytosolic protein that plays a critical role in intracellular copper homeostasis by delivering copper ions to the copper-transporting ATPases, ATP7A and ATP7B (UniProt: P55957). These transporters then move copper into the secretory pathway for incorporation into cuproenzymes or for biliary excretion (PubMed: 11553613). Beyond its chaperone function, ATOX1 acts as a copper-dependent transcription factor and a modulator of various signaling pathways involved in cell proliferation, migration, and angiogenesis (PubMed: 30610235). In the context of oncology, ATOX1 is frequently overexpressed in various cancers and is associated with poor prognosis, as it supports the high copper demands of rapidly dividing cells and facilitates metastasis (PubMed: 25703317). Therapeutic strategies targeting ATOX1 include small molecule inhibitors like DC-AC01 that block its copper-binding domain or its interaction with downstream transporters, thereby disrupting the copper supply chain essential for tumor progression (PubMed: 25703317). Additionally, ATOX1 has been shown to bind platinum-based chemotherapeutics like cisplatin, potentially contributing to drug resistance by sequestering the drug before it reaches the nucleus (PubMed: 29330111).

Other names

HAH1Copper transport protein ATOX1Metal transport protein ATX1ATX1 homolog

Inhibition of copper transfer to P-type ATPases (ATP7A and ATP7B) and disruption of copper-dependent signaling pathways (PubMed: 25703317).