Metallothionein-3 (MT-3) (MT-3)

Metallothionein-3 (MT-3), also known as Growth Inhibitory Factor (GIF), is a small, cysteine-rich, metal-binding protein primarily expressed in the central nervous system [1, 6, 8]. Unlike other members of the metallothionein family, MT-3 possesses a unique ability to inhibit neurite outgrowth and neuronal survival, a function attributed to specific structural motifs like the TCPCP sequence in its N-terminal domain [1, 7, 12]. It plays a critical role in maintaining zinc and copper homeostasis and acts as a potent antioxidant by scavenging reactive oxygen species [1, 10, 13]. In neurodegenerative conditions such as Alzheimer's disease, MT-3 levels are significantly reduced, leading to impaired metal regulation and increased oxidative stress [1, 10, 13]. Conversely, in certain cancers like hepatocellular carcinoma and acute myeloid leukemia, MT-3 expression is often dysregulated and can contribute to drug resistance or act as a tumor suppressor [15, 16]. Therapeutic strategies targeting MT-3 focus on modulating its metal-binding capacity or restoring its expression to mitigate neurodegeneration and improve treatment outcomes in oncology [1, 14, 16].

Other names

Growth inhibitory factorGIFGIFBMetallothionein-IIIMT-IIIMT3

Metal sequestration and release, reactive oxygen species scavenging, modulation of lysosomal pH, and interaction with cytoskeletal and signaling proteins [1, 12, 13, 14].