A PROTEOLYTIC SYSTEM THAT COMPENSATES FOR LOSS OF PROTEASOME FUNCTION

Proteolysis is essential for the execution of many cellular functions. These include removal of incorrectly folded or damaged proteins(1), t he activation of transcription factors(2), the ordered degradation of proteins involved in cell cycle control(3), and the generation of pept ides destined for presentation by class I molecules of the major histo compatibility complex(4). A multisubunit protease complex, the proteas ome(5), accomplishes these tasks. Here we show that in mammalian cells inactivation of the proteasome by covalent inhibitors allows the outg rowth of inhibitor-resistant cells. The growth of such adapted cells i s apparently maintained by the induction of other proteolytic systems that compensate for the loss of proteasomal activity.