Regulation of protein degradation rates in eukaryotes

Abstract

In order to survive, all cells must be able to adapt to a changing extracellular environment. A l~ey element in a cell's response to exogenous stimuli is its ability to change the concentration of specific cellular proteins. Since the concentration of a protein is determined by the balance between its rates of synthesis and degradation, the cell can alter either parameter. Numerous examples have been described where the levels of specific proteins are altered by changing the rates of protein synthesis through a variety of transcriptional and/or translational mechanisms. However, in many instances the rate of degradation of a protein is also regulated, and for some proteins alterations in degradation rate are quantitatively more important than changes in protein synthesis. To illustrate these points we have compiled published data for the regulation of 12 liver enzymes during starvation or acute diabetes (Table 1). Although overall rates of proteolysis are increased under these conditions, the changes in degradation of indMdual proteins are heterogeneous. The observed changes in enzyme concentration may be due to alterations in rates of synthesis only (the first four enzymes listed in Table 1), in degradative rates only (the last two enzymes listed in Table 1), or in both rates of synthesis and degradation (the remaining enzymes listed in Table 1). In the first section of this review we will present recent examples of the control of individual protein levels by regulating the degradation rate of the protein. In most of these examples the degradative pathway involved is unknown, but these cases illustrate reasons why control of a specific protein's degradation rate is often crucial for cellular response to changing extracellular stimuli.