Proteasomal degradation of damaged polyubiquitin

Ubiquitination is one of the most important post-translational modifications of proteins and is involved in various cellular activities, such as proteasomal protein degradation. Ubiquitination is performed via sequential reactions of three enzymes producing polyubiquitin chains, while deubiquitination enzymes can reverse this process, making it possible to recycle ubiquitin molecules. However, such repeated use may seriously damage ubiquitin molecules and result in cell toxicity. Here we show efficient, selective proteasomal degradation of damaged polyubiquitin chains both in vitro and in vivo. However, the degradation efficiency of the damaged polyubiquitin strongly depends on the extent and location of damage to polyubiquitin. Moderate damage at the C-terminal ubiquitin moiety accelerates the degradation of polyubiquitin chains, whereas other damaged ubiquitin escapes from proteasomal degradation. We suggest that the cell can cope with damaged ubiquitin by the cooperative actions of the proteasome and autophagy.