Module description: Protein molecules are continuously synthesised and degraded in all living organisms. Protein degradation plays an important role in cell cycle, etc. The degradation rates of proteins are important in determining their cellular concentrations. Protein degradation exhibits first-order kinetics unlike protein synthesis, which is zero-order. Protein degradation is energy dependent, requiring ATP, and is limited by the concentration of the reactants, whereas protein synthesis cannot be completed in the absence of any one of the necessary reactants. Proteins breakdown at rates, ranging from 100% per hour to less than 10% per hour and their half-lives (time taken for loss of half the protein molecules) vary between 24h and 72h. Regulatory enzymes and proteins have much shorter half-lives of the order of 5-120min. Protein breakdown can take place in the mitochondria, chloroplasts, the lumen of the endoplasmic reticulum and the endosomes, but occurs most commonly in one of two major sites of intracellular proteolysis, lysosomes and the cytosol. Most non-selective protein degradation takes place in the lysosomes, where changes in the supply of nutrients and growth factors can influence the rates of protein breakdown. Proteins enter lysosomes by macroautophagy, that is the enclosure of a volume of the cytoplasm by an intracellular membrane. Short-lived regulatory proteins are degraded in the cytosol by local proteolytic mechanisms. All short-lived proteins are thought to contain recognition signals that mark them for early degradation. One commonly employed method is the selective labelling of targeted proteins by ubiquitin molecules. Ubiquitin, a protein of 76 amino acids, binds covalently to available lysine residues on target proteins, which are then recognised by proteases. A number of molecular recognition signals for intracellular protein degradation have been identified, and there are likely to be others as yet undiscovered. Additional degradative mechanisms exist for the identification and rapid degradation of proteins that contain translational or post-translational errors, or have been damaged in some way. The degradation of red blood cells is unusual in that it is age dependent. As a consequence haemoglobin also exhibits age-linked degradation. Beatrice Gorinsky, 1994[Excerpted from http://www.biochem.emory.edu/labs/genekdw/protdeg2000/intro.html

General introduction to Protein degradation and concentrating on proteosome pathways