Destruction of Oxidized Proteins

Kelvin J. A. Davies
University of Southern California
R01ES03598

Background: The accumulation of damaged proteins is a characteristic of aging cells and many age-related conditions such as Alzheimer's disease. Unless these proteins are repaired or removed from cells, they often impair proper cell function and can lead to cell death. Cells contain complexes of enzymes designed to breakdown these proteins known as proteasomes. Proteasomes not only degrade harmful accumulations of damaged proteins, but they also breakdown short-lived regulatory proteins important in a variety of basic cellular processes.

Advance: For the most part, proteasomes recognize, unfold, and digest proteins that have been marked for degradation by the attachment of multiple molecules of ubiquitin. This ubiquitin-proteasome pathway functions widely in intracellular protein turnover. However, recent research sponsored by NIEHS at the University of Southern California has shown that at form of the proteasome known as 20 S can carry out protein degradation without the ubiquitinylation. This research, done in intact cells in culture, builds on previous findings in this laboratory.

Implication: The focus of this research team is the role of free radicals and oxidative stress in biology. In particular the lab is focused on oxidative stress during aging and aging pathologies such as Parkinson and Alzheimer's diseases. The results reported here describe a novel method for the destruction and removal of oxidatively damaged proteins. Although very basic in nature, this study provides insight into normal cell functioning, may lead to discoveries of how disease of aging impair these functions, and possibly provide clues to how these diseases may be prevented or treated.

Citation: Shringarpure R, Grune T, Mehlhase J, Davies KJ. Ubiquitin conjugation is not required for the degradation of oxidized proteins by proteasome. J Biol Chem. 2003 Jan 3; 278(1):311-8.