Valosin-containing protein (VCP) mRNA (VCP mRNA)

Valosin-containing protein (VCP), also known as p97, is a highly conserved hexameric AAA+ ATPase that serves as a central regulator of protein homeostasis by extracting ubiquitinated proteins from membranes or macromolecular complexes for degradation by the proteasome. Targeting the VCP mRNA represents a therapeutic strategy to modulate the levels of the VCP protein, which is frequently overexpressed in various cancers to support rapid proliferation and stress tolerance. In neurodegenerative contexts, such as Amyotrophic Lateral Sclerosis (ALS) and Inclusion Body Myopathy with Paget disease of bone and Frontotemporal Dementia (IBMPFD), mutations in the VCP gene lead to toxic gain-of-function or loss-of-function effects that result in protein aggregation and cellular dysfunction. Therapeutic modalities like antisense oligonucleotides (ASOs) are designed to bind specifically to VCP mRNA, triggering its degradation and subsequently reducing the production of the VCP protein to restore cellular balance or induce apoptosis in malignant cells. While promising, targeting VCP mRNA requires careful calibration due to the protein's essential role in fundamental cellular processes across multiple tissues.

Other names

p97 mRNATransitional endoplasmic reticulum ATPase mRNACDC48 mRNATERA mRNA

RNase H-mediated degradation of mRNA, RNA interference (RNAi), Translation inhibition