Structural and functional implications of phosphorylation and acetylation in the regulation of the AAA+ protein p97.
p97, also known as VCP (valosin-containing protein), is a hexameric AAA+ ATPase that participates in a variety of cellular processes. It is believed that p97 mediates these processes through the binding of various adaptor proteins. Many factors govern adaptor binding and the regulatory mechanisms are not yet well understood. Sites of phosphorylation and acetylation on p97 have been identified and such post-translational modifications may be involved in regulating p97 function. Phosphorylation and, to a lesser extent, acetylation of p97 have been shown to modify its properties - for example, by modulating adaptor binding and directing subcellular localization. These modifications have been implicated in a number of p97-mediated processes, including misfolded protein degradation, membrane fusion, and transcription factor activation. This review describes the known phosphorylation and acetylation sites on p97 and discusses their possible structural and functional implications.
Division of Molecular Biosciences, Centre for Structural Biology, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United Kingdom.
Caroline A
CA
Ewens
Patrik
P
Kloppsteck
Andreas
A
Förster
Xiaodong
X
Zhang
Paul S
PS
Freemont
D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics; D011487:Protein Conformation; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D000074405:Valosin Containing Protein
D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein