Regulation of intracellular protein turnover: covalent modification as a mechanism of marking proteins for degradation.

Abstract

Mixed-function oxidation systems have an ubiquitous distribution, and many of them can cause oxidative modification of proteins presumably by the interaction of active oxygen species, for example, hydrogen peroxide, superoxide anion, singlet oxygen, hydroxyl radical, with specific amino acid residues in the protein. It is well known that active oxygen species, which can also be produced in vivo during respiration, can affect other cell components causing both lipid peroxidation and DNA damage. However, the effect of radical attack on proteins has only recently been investigated. Protein breakdown can be highly regulated by factors which affect the stability of proteins to modification, or the activity of marking reactions, and the activity of individual proteases and different degradation systems. In mammalian cells, the contribution of the different degradation systems probably varies with changes in hormonal and nutritional states. The rate of degradation may be controlled by uptake into lysosomes or by factors which influence the activity of non-lysosomal proteases.