|Time for the ubiquitin-proteasome system
Most likely, dysfunction of the ubiquitin-proteasome system (UPS) contributes to the neuropathogenesis of various types of conformational diseases (for example, Alzheimer, Parkinson, and Huntington diseases). The past decade has revealed a surprising complexity of this system, especially with regard to enzymes such as E2 conjugating enzymes (for example E2-25K-Hip2) and the numerous E3 ligating proteins (for example CHIP, parkin). For a good review, see Pickart and Cohen, 2004
). In addition, other proteolytic factors were identified, for example, CDC48/p97. These were coined “E4 enzymes.” They escort ubiquitinated proteins to the proteasome, where they are then degraded. This paper places these various E4 factors in a sequential order in yeast studies, as illustrated in their figure 7 on page 81 (see also commentary by Huibregtse, 2005
It is now time to verify the relevance of these E4 factors for neuropathogenesis in neuronal...