How does the cell know which proteins to degrade, and when?

The proper functioning of the cell requires careful control of the levels of important structural proteins, enzymes, and regulatory proteins. The only way that cells can reduce the steady state level of a particular protein is by proteolytic degradation. Thus, complex and highly-regulated mechanisms have been evolved to accomplish this degradation.

Recent reviews on intracellular proteolysis

An additional role of intracellular proteolysis is in the stress-response. Cells which are subject to stress such as starvation, heat-shock, chemical insult or mutation respond by increasing the rates of proteolysis. One function of this enhanced proteolysis is to salvage amino acids from non-essential proteins. These amino acids can then be reutilized in the synthesis of essential proteins or metabolized directly to provide energy. Another function is in the repair of damage caused by the stress. For example, oxidative stress has been shown to damage a variety of proteins and cause them to be rapidly degraded.

Recent reviews on heat-shock and proteolysis of damaged proteins

Some proteins are genetically unstable. The mechanisms by which proteins are selected for degradation by the cell are poorly understood. There appear to be signal sequences which target proteins to degradation. These can be part of the protein structure, or added post-translationally.

Recent reviws on targeting signals for proteolysis


How does the cell know which proteins to degrade, and when?