Cisplatin is a widely used chemotherapeutic agent for treatment of ovarian, testicular, lung, and stomach cancers. The initial response to the drug is robust; however, tumor cells commonly develop resistance to cisplatin, which complicates treatment. Recently, overexpression of the Cu-ATPase ATP7B in ovary cells was linked to the increased cellular resistance to cisplatin; and the role for Cu-A...

The Wilson protein (ATP7B) is a copper-translocating P-type ATPase that mediates the excretion of excess copper from hepatocytes into bile. Excess copper causes the protein to traffic from the TGN (trans-Golgi network) to subapical vesicles. Using site-directed mutagenesis, mutations known or predicted to abrogate catalytic activity (copper translocation) were introduced into ATP7B and the effe...

BACKGROUND/AIMS Wilson disease (WD, MIM# 277900) is an autosomal recessive disorder of copper transport resulting from the defective function of a copper transporting P-type ATPase. Detecting mutations and single nucleotide polymorphisms (SNPs) of the ATP7B gene in Turkish pediatric WD patients (n=32) and controls (n=52) is the aim of this research. MATERIALS AND METHODS For screening mutatio...

BACKGROUND Wilson's disease (WD) is a genetic disorder involving the metabolism of copper. WD patients exhibit a wide range of disease phenotypes, including Kayser-Fleischer rings in the cornea, predominant progressive hepatic disease, neurological diseases, and/or psychiatric illnesses, among others. Patients with exon12 mutations of the ATP7B gene have progressive hepatic disease. An ATP7B ge...

Copper is essential for brain metabolism, serving as a cofactor to superoxide dismutase, dopamine-beta-hydroxylase, amyloid precursor protein, ceruloplasmin, and other proteins required for normal brain function. The copper-transporting ATPases ATP7A and ATP7B play a central role in distribution of copper in the central nervous system; genetic mutations in ATP7A and ATP7B lead to severe neurode...

We have previously developed a functional assay in yeast for the copper transporter, ATP7B, defective in Wilson disease (WND). Analysis of WND variant ATP7B proteins revealed that several were able to completely, or nearly completely, complement a mutant yeast strain in which the ATP7B ortholog CCC2 was disrupted, indicating that these ATP7B proteins retained copper transport activity. We analy...

OBJECTIVE To analyze ATP7B mutations in Wilson's disease (WD) patients from the Indian subcontinent and to correlate these with WD phenotype. METHODS We studied 27 WD patients from 25 unrelated families. Twenty-two families were from three southern Indian states - Tamil Nadu andhra Pradesh and Kerala. We applied conformation- sensitive gel electrophoresis (CSGE) to screen for the mutations in...

ATP7B is a copper-transporting P-type ATPase present predominantly in liver. In basal copper, hepatic ATP7B is in a post-trans-Golgi network (TGN) compartment where it loads cytoplasmic Cu(I) onto newly synthesized ceruloplasmin. When copper levels rise, the protein redistributes via unique vesicles to the apical periphery where it exports intracellular Cu(I) into bile. We want to understand th...

ATP7A and ATP7B are copper-transporting P-type ATPases that are essential to eukaryotic copper homeostasis and must traffic between intracellular compartments to carry out their functions. Previously, we identified a nine-amino acid sequence (F37-E45) in the NH(2) terminus of ATP7B that is required to retain the protein in the Golgi when copper levels are low and target it apically in polarized...

Neurons are highly polarized cells having distinct somatodendritic and axonal domains. Here we report that polarized sorting of the Cu(2+) transporter ATP7B and the vesicle-SNARE VAMP4 to the somatodendritic domain of rat hippocampal neurons is mediated by recognition of dileucine-based signals in the cytosolic domains of the proteins by the σ1 subunit of the clathrin adaptor AP-1. Under basal ...