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Updated: Oct 29, 2025

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
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Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

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VCP maintains nuclear size by regulating the DNA damage-associated MDC1-p53-autophagy axis in Drosophila

Ya-Chu Chang1,2, Yu-Xiang Peng1, Bo-Hua Yu1

  • 1Institute of Biotechnology, Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan.

Nature Communications
|July 13, 2021
PubMed

Insights

Disrupting valosin-containing protein (VCP) function in Drosophila causes nuclear size increase by accumulating MDC1 and stabilizing p53A. This suggests VCP is crucial for maintaining nuclear size homeostasis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Nuclear size is physiologically significant and linked to malignant transformation.
  • The precise mechanisms underlying nuclear size anomalies remain unclear.

Purpose of the Study:

  • To investigate the role of valosin-containing protein (VCP/TER94) in regulating nuclear size.
  • To elucidate the molecular mechanisms connecting VCP function to nuclear size control.

Main Methods:

  • Expression of dominant-negative TER94 mutants in Drosophila photoreceptors.
  • Analysis of VCP, MDC1, and p53A protein levels and interactions.
  • Assessment of nuclear size changes and autophagic flux.

Main Results:

  • Disruption of VCP function leads to progressive nuclear size increase.
  • Loss of VCP function causes accumulation of MDC1, a VCP substrate.
  • MDC1 accumulation stabilizes p53A, contributing to nuclear enlargement.

Conclusions:

  • VCP is essential for maintaining nuclear size homeostasis.
  • VCP regulates nuclear size by controlling MDC1 and p53A levels.
  • Impaired VCP function may lead to aberrant nuclear size increase via disrupted autophagic flux.

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