A proteolytic system that compensates for loss of proteasome function

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Abstract
Proteolysis is essential for the execution of many cellular functions. These include removal of incorrectly folded or damaged proteins1, the activation of transcription factors2, the ordered degradation of proteins involved in cell cycle control3, and the generation of peptides destined for presentation by class I molecules of the major histocompatibility complex4. A multisubunit protease complex, the proteasome5, accomplishes these tasks. Here we show that in mammalian cells inactivation of the proteasome by covalent inhibitors allows the outgrowth of inhibitor-resistant cells. The growth of such adapted cells is apparently maintained by the induction of other proteolytic systems that compensate for the loss of proteasomal activity.