The 26 S proteasome: From basic mechanisms to drug targeting

The regulated degradation of proteins within eukaryotes and bacterial cells is catalyzed primarily by large multimeric proteases in ATP-dependent manner. In eukaryotes, the 26 S proteasome is essential for the rapid destruction of key regulatory proteins, such as cell cycle regulators and transcription factors, whose fast and tuned elimination is necessary for the proper control of the fundamental cell processes they regulate. In addition, the 26 S proteasome is responsible for cell quality control by eliminating defective proteins from the cytosol and endoplasmic reticulum. These defective proteins can be misfolded proteins, nascent prematurely terminated polypeptides, or proteins that fail to assemble into complexes. These diverse activities and its central role in apoptosis have made the proteasome an important target for drug development, in particular to combat malignancies.