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The VCP/p97 system at a glance: connecting cellular function to disease pathogenesis.

Hemmo Meyer1, Conrad C Weihl2

  • 1Centre for Medical Biotechnology, Faculty of Biology, University of Duisburg-Essen, 45117 Essen, Germany hemmo.meyer@uni-due.de weihlc@neuro.wustl.edu.

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The ATPase valosin-containing protein (VCP)/p97 is crucial for cellular functions and proteostasis. This review explores its role in disease and its emerging links to RNA biology and stress responses.

Keywords:
ALSCdc48IBMPFDUbiquitinVCPp97

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Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The ATPase valosin-containing protein (VCP)/p97 is a key component of the ubiquitin system.
  • VCP/p97, with its cofactors, regulates diverse cellular processes, impacting proteostasis, signaling, and genomic stability.

Purpose of the Study:

  • To provide an overview of the VCP/p97 system.
  • To discuss the molecular basis of VCP/p97-associated diseases.
  • To highlight novel connections between VCP/p97, the translational stress response, and RNA biology.

Main Methods:

  • Literature review and synthesis of existing research.
  • Discussion of pathogenic mechanisms in VCP/p97-related disorders.
  • Exploration of emerging evidence linking VCP/p97 to RNA metabolism and stress granules.

Main Results:

  • VCP/p97 plays a central role in maintaining cellular homeostasis and protein quality control.
  • Dysfunction of VCP/p97 is implicated in various degenerative diseases.
  • New research reveals VCP/p97's involvement in regulating the cellular response to stress and its interaction with RNA granules.

Conclusions:

  • The VCP/p97 ATPase complex is vital for cellular physiology and proteostasis.
  • Understanding VCP/p97's role in disease pathogenesis is critical for therapeutic development.
  • The VCP/p97 system's intricate connections to RNA biology and translational control offer new avenues for research and potential therapeutic strategies.