p97

p97 (also referred to as VCP) is a highly conserved and abundant AAA+ (ATPases associated with diverse cellular activities) ATPase that plays an essential role in cellular proteostasis. p97 participates in a large number of important cellular activities, including (i) proteasomal degradation, through its roles in extracting proteins from membranes or molecular complexes; (ii) lysosomal degradation via autophagy and endolysosomal sorting; (iii) membrane fusion; and (iv) regulation of intracellular signaling, cell proliferation, and survival. These diverse cellular functions are powered by the chemical energy from ATP hydrolysis and coordinated through the interaction of p97 with as many as 40 cofactors that recruit it to specific subcellular locations and to designated substrates for their remodeling and processing.

Mutations in p97 have been linked to a number of neurodegenerative diseases, and overexpression of wild type p97 is observed in numerous cancers. Furthermore, p97 activity has been shown to be essential for the replication of certain viruses, including poliovirus, herpes simplex virus (HSV), cytomegalovirus (CMV), and influenza. These observations highlight the potential for targeting p97 as a therapeutic approach in neurodegeneration, cancer, and certain infectious diseases.