Cdc48: a power machine in protein degradation

Cdc48 is an essential, highly prominent ATP driven machine in eukaryotic cells. Physiological function of Cdc48 has been found in a multitude of cellular processes, for instance cell cycle progression, homotypic membrane fusion, chromatin remodeling, transcriptional and metabolic regulation, and many others. The molecular function of Cdc48 is arguably best understood in endoplasmic reticulum-associated protein degradation by the ubiquitin proteasome system. In this review, we summarize the general characteristics of Cdc48/p97 and the most recent results on the molecular function of Cdc48 in some of the above processes, which were found to finally end in proteolysis-connected pathways, either involving the proteasome or autophagocytosis-mediated lysosomal degradation.