E2 E3 E2 E3 E2 E1 into other proteins. Most proteins are replaced every few days, even in cells that themselves divide rarely, such as those in the liver or nervous system. And different proteins are degraded at widely differing rates: some have halflives as short as 20 minutes, whereas others in the same cell may last for days or weeks. These rates of breakdown can change drastically according to changing conditions in our bodies. At first glance, such continuous destruction of cell constituents appears very wasteful, but it serves a number of essential functions. Degrading a crucial enzyme or regulatory protein, for example, is a common mechanism that cells use to slow or stop a biochemical reaction. On the other hand, many cellular processes are activated by the degradation of a critical inhibitory protein, just as water flows out of a bathtub when you remove the stopper. This rapid elimination of regulatory proteins is particularly important in timing the transitions between the stages of the cycle that drives cell division [see box on page 72].

Protein degradation also plays special roles in the overall regulation of body metabolism. In times of need, such as malnourishment or disease, the proteasome pathway becomes more active in our muscles, providing amino acids that can be converted into glucose and burned for energy. This excessive protein breakdown accounts for the muscle wasting and weakness seen in starving individuals and those with advanced cancer, AIDS and untreated diabetes. Our immune system, in its constant search to eliminate virus-infected or cancerous cells, also depends on proteasomes to generate the flags that distinguish such dangerous cells. In this process, the immune system functions like a suspicious landlady checking whether