Identification of p38 MAPK and JNK as new targets for correction of Wilson disease-causing ATP7B mutants.

ABSTRACT:

Unlabelled

Wilson disease (WD) is an autosomal recessive disorder that is caused by the toxic accumulation of copper (Cu) in the liver. The ATP7B gene, which is mutated in WD, encodes a multitransmembrane domain adenosine triphosphatase that traffics from the trans-Golgi network to the canalicular area of hepatocytes, where it facilitates excretion of excess Cu into the bile. Several ATP7B mutations, including H1069Q and R778L that are two of the most frequent variants, result in protein products, which, although still functional, remain in the endoplasmic reticulum. Thus, they fail to reach Cu excretion sites, resulting in the toxic buildup of Cu in the liver of WD patients. Therefore, correcting the location of these mutants by leading them to the appropriate functional sites in

SUBMITTER: Chesi G 

PROVIDER: S-EPMC5066671 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature