p97: The cell's molecular purgatory?
The multifunctional AAA-ATPase p97/VCP is one of the most extensively studied members of this protein family, yet it presents the field with many perplexing questions surrounding its mechanism of substrate engagement and processing. Recent discoveries have unmasked a new purgatorial identity for this molecule in the ubiquitin-proteasome pathway, specifically its role in linking ubiquitylated substrates with competing ubiquitin conjugation and deconjugation machineries. Furthermore, biochemical studies surprisingly identify the C-terminal D2 ring as essential for substrate interaction, thus bringing p97 one step closer to its prokaryotic AAA protease relatives.
Halawani
Dalia
D
Department of Anatomy and Cell Biology, McGill University, 3640 University Street, Montreal, QC H3A 2B2, Canada.
Latterich
Martin
M
Department of Anatomy and Cell Biology, McGill University, 3640 University Street, Montreal, QC H3A 2B2, Canada. Electronic address: martin.latterich@mcgill.ca.
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011387:Prokaryotic Cells / Q000201:enzymology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D025801:Ubiquitin / Q000378:metabolism*; D000074405:Valosin Containing Protein
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C404942:p97 ATPase; C000614178:VCP protein, human; D000074405:Valosin Containing Protein