p97s

p97s, also known as valosin-containing proteins (VCP) or N-terminal deletion protein (NTD-protein), are a class of highly conserved AAA+ adenosine triphosphatases (ATPases) found in all eukaryotes. These proteins are essential molecular machines involved in a wide range of cellular processes. The core function of p97s revolves around their ability to bind to and unfold ubiquitously tagged proteins, particularly ubiquitinated substrates. This process is ATP-dependent, meaning the protein uses energy derived from ATP hydrolysis to drive conformational changes and exert mechanical force.

The cellular roles of p97s are diverse and critical for cell viability. They play significant roles in protein degradation pathways, including the ubiquitin-proteasome system, where they extract ubiquitinated proteins from cellular compartments for degradation. Beyond protein degradation, p97s are implicated in DNA repair, membrane fusion, organelle biogenesis and homeostasis, and the regulation of various signaling pathways. Their involvement in such fundamental processes highlights their central importance in maintaining cellular integrity and function. Dysregulation of p97 activity has been linked to a variety of human diseases, including neurodegenerative disorders, cancer, and muscle diseases, making it a subject of intense research interest for therapeutic development.