VCPp97

VCPp97, also known as VCP-associated protein p97 or p97, is a ubiquitous and highly conserved protein found in all eukaryotes. It belongs to the AAA+ ATPase superfamily, a group of proteins characterized by their ability to hydrolyze ATP and utilize the energy released for various cellular processes. VCPp97 is a core component of the cellular machinery involved in protein homeostasis, playing critical roles in protein degradation, DNA repair, membrane fusion, and organelle biogenesis.

The protein functions as a hexameric ring structure, with each subunit possessing two AAA+ ATPase domains. This structure allows VCPp97 to interact with a wide range of substrate proteins and cofactors, facilitating their unfolding, translocation, or ubiquitination. Its involvement in the ubiquitin-proteasome system is particularly prominent, where it acts as an adaptor to recruit ubiquitinated substrates to the proteasome for degradation.

Dysregulation of VCPp97 activity has been implicated in a variety of human diseases, including neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, as well as cancer and developmental abnormalities. These links highlight the essential nature of VCPp97 in maintaining cellular health and the devastating consequences of its malfunction. Ongoing research continues to explore the diverse functions of VCPp97 and its potential as a therapeutic target for these diseases.