Abstract
The Wilson disease protein (ATP7B) is a copper-transporting ATPase that is responsible for regulating copper homeostasis in human tissues. ATP7B is associated with cancer resistance to cisplatin, one of the most widely used anticancer drugs. This minireview discusses the possible mechanisms of tumor resistance to cisplatin mediated by ATP7B. Cisplatin binds to the N-terminal cytosolic domain of ATP7B, which contains multiple copper-binding sites. Active platinum efflux catalyzed by ATP7B is unlikely to significantly contribute to cisplatin resistance in vivo. Transient platinum sequestration in the metal-binding domain followed by transfer to an acceptor protein or a low molecular weight compound is proposed as an alternative mechanism of cisplatin detoxification in the cell.
Publication types
-
Research Support, Non-U.S. Gov't
-
Review
MeSH terms
-
Adenosine Triphosphatases / chemistry
-
Adenosine Triphosphatases / genetics
-
Adenosine Triphosphatases / metabolism*
-
Antineoplastic Agents / therapeutic use*
-
Binding Sites
-
Biological Transport
-
Cation Transport Proteins / chemistry
-
Cation Transport Proteins / genetics
-
Cation Transport Proteins / metabolism*
-
Cisplatin / therapeutic use*
-
Copper / metabolism*
-
Copper-Transporting ATPases
-
Drug Resistance, Neoplasm / physiology*
-
Humans
-
Models, Molecular
-
Molecular Structure
-
Neoplasms / drug therapy*
-
Neoplasms / physiopathology*
-
Platinum / metabolism
-
Protein Binding
Substances
-
Antineoplastic Agents
-
Cation Transport Proteins
-
Platinum
-
Copper
-
Adenosine Triphosphatases
-
ATP7B protein, human
-
Copper-Transporting ATPases
-
Cisplatin