A proteolytic system that compensates for loss of proteasome function

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Proteolysis is essential for the execution of many cellular functions.These include removal of incorrectly folded or damaged proteins [1], the activation of transcription factors [2], the ordered degradation of proteins involved in cell cycle control [3], and the generation of peptides destined for presentation by class I molecules of the major histocompatibility complex [4]. A multisubunit protease complex, the proteasome [5], 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.

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