The 26S proteasome plays a critical role in many cellular processes by degrading a wide range of both short-lived and long-lived proteins. In this review, proteasome structure and the mechanisms of substrates targeting to the 26S proteasome are described. In addition, this review focuses on the cellular functions that are affected after inhibition of the proteasome, including immune-response, cell-cycle, and transcription. The proteasome is involved in these cellular processes because it degrades numerous short-lived proteins and regulatory proteins that control these cellular functions. Even though it is known that inhibition of the 26S proteasome results in the induction of the synthesis of heat-shock proteins (e.g., Hsp 70), several groups indicated that 26S proteasome inhibition also causes a significant loss of global protein synthesis activity in a very short time.

The 26S proteasome plays a critical role in many cellular processes by degrading a wide range of both short-lived and long-lived proteins. In this review, proteasome structure and the mechanisms of substrates targeting to the 26S proteasome are described. In addition, this review focuses on the cellular functions that are affected after inhibition of the proteasome, including immune-response, cell-cycle, and transcription. The proteasome is involved in these cellular processes because it degrades numerous short-lived proteins and regulatory proteins that control these cellular functions. Even though it is known that inhibition of the 26S proteasome results in the induction of the synthesis of heat-shock proteins (e.g., Hsp 70), several groups indicated that 26S proteasome inhibition also causes a significant loss of global protein synthesis activity in a very short time.