Evidence for the Deregulation of Protein Turnover Pathways in Atm-Deficient Mouse Cerebellum: An Organotypic Study.
J Neuropathol Exp Neurol 2017 May 23. Epub 2017 May 23.
From the Department of Biochemistry & Molecular Biology, LSU Health Sciences Center-School of Medicine, New Orleans, Louisiana (CDK, RER, MAJ, SDD); and Biostatistics Program, LSU Health Sciences Center-School of Public Health, New Orleans, Louisiana (ZF).
Interferon-stimulated gene 15 (ISG15), an antagonist of the ubiquitin pathway, is elevated in cells and brain tissues obtained from ataxia telangiectasia (A-T) patients. Previous studies reveal that an elevated ISG15 pathway inhibits ubiquitin-dependent protein degradation, leading to activation of basal autophagy as a compensatory mechanism for protein turnover in A-T cells. Also, genotoxic stress (ultraviolet [UV] radiation) deregulates autophagy and induces aberrant degradation of ubiquitylated proteins in A-T cells. Read More