Metallothionein-1 (MT-1) (MT-1)

Metallothionein-1 (MT-1) is a low molecular weight, cysteine-rich protein that belongs to a family of stress-response proteins primarily involved in metal ion homeostasis and detoxification [1, 11]. In humans, MT-1 consists of multiple functional isoforms, such as MT1A and MT1G, which are induced by stressors including heavy metals, oxidative stress, and glucocorticoids [1, 8]. The protein functions by sequestering essential trace metals like zinc and copper, as well as toxic metals like cadmium and mercury, through high-affinity thiolate ligands [7, 13, 15]. Beyond metal metabolism, MT-1 serves as a potent antioxidant by scavenging reactive oxygen species (ROS), thereby protecting cells from oxidative damage and apoptosis [7, 11]. In clinical medicine, MT-1 is a primary target in Wilson’s disease, where zinc therapy is used to induce intestinal MT-1 expression, which then binds dietary copper and prevents its systemic absorption [17, 19, 20]. Conversely, in oncology, high MT-1 levels are a significant therapeutic challenge because the protein can sequester and neutralize platinum-based chemotherapies like cisplatin, leading to acquired drug resistance [10, 21]. Recent evidence also identifies extracellular MT-1 as a mediator of pathological immune cell infiltration in autoimmune conditions like Type 1 Diabetes, making it a target for emerging monoclonal antibody therapies [2, 5, 6].

Other names

MT1MT-IMetallothionein-1 familyMetallothionein-1AMetallothionein-1BMetallothionein-1EMetallothionein-1FMetallothionein-1GMetallothionein-1HMetallothionein-1MMetallothionein-1X

Drugs target Metallothionein-1 through the induction of its expression to chelate and sequester copper in the intestine, the sequestration and inactivation of platinum-based chemotherapeutic agents, or the neutralization of extracellular isoforms to reduce immune cell infiltration and inflammatory signaling.