Cdc48 (p97): a "molecular gearbox" in the ubiquitin pathway?
Cdc48 (p97), a conserved chaperone-like ATPase of eukaryotic cells, has attracted attention recently because of its wide range of cellular functions. Cdc48 is intimately linked to the ubiquitin pathway because its primary action is to segregate ubiquitinated substrates from unmodified partners. This 'segregase' activity is crucial for certain proteasomal degradation pathways and for some nonproteolytic functions of ubiquitin. Cdc48 associates not only with different 'substrate-recruiting cofactors' but also with distinct 'substrate-processing cofactors'. The latter proteins control the degree of ubiquitination of bound substrates by shifting the polyubiquitination reaction into 'forward', 'neutral' or 'reverse'. We discuss how Cdc48 might use this 'gearbox activity' to control protein fate and propose a similar mode of action for the 19S cap of the proteasome.
Jentsch
Stefan
S
Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany. Jentsch@biochem.mpg.de
Rumpf
Sebastian
S
D000251:Adenosine Triphosphatases / Q000502:physiology*; D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis; D008561:Membrane Fusion / Q000502:physiology; D053858:Metabolic Networks and Pathways / Q000502:physiology; D018832:Molecular Chaperones / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin / Q000378:metabolism*; D000074405:Valosin Containing Protein
D018797:Cell Cycle Proteins; D005231:Fatty Acids, Unsaturated; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C000614177:CDC48 protein, S cerevisiae; D000074405:Valosin Containing Protein