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Published on: August 4, 2019

Myosin VI is a mediator of the p53-dependent cell survival pathway

Eun Joo Jung1, Gang Liu, Wenjing Zhou

  • 1Department of Cell Biology, MCLM 660, 1530 3rd Ave. S, Birmingham, AL 35294-0005, USA.

Molecular and Cellular Biology
|March 2, 2006
PubMed

Insights

Myosin VI is regulated by DNA damage via p53, playing a key role in cell survival. This study reveals its novel function in the p53-dependent prosurvival pathway and Golgi complex integrity.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Myosin VI is an unconventional motor protein implicated in sensorineural deafness and hypertrophic cardiomyopathy.
  • It plays a role in Golgi complex protein trafficking and homeostasis.
  • Regulation and function of Myosin VI in DNA damage response remain largely unknown.

Purpose of the Study:

  • To investigate the regulation of Myosin VI by DNA damage.
  • To determine Myosin VI's function in the DNA damage response.
  • To elucidate the relationship between Myosin VI, p53, and Golgi complex integrity.

Main Methods:

  • p53-dependent gene induction analysis.
  • Chromatin immunoprecipitation (ChIP) assay to assess p53 binding to the Myosin VI promoter.
  • Immunofluorescence microscopy to track intracellular localization of Myosin VI.
  • Myosin VI knockdown experiments followed by apoptosis assays and Golgi integrity assessment.

Main Results:

  • Myosin VI is induced by DNA damage in a p53-dependent manner.
  • p53 directly binds to and activates the Myosin VI gene promoter.
  • DNA damage and p53 alter Myosin VI localization from endocytic vesicles and cytosol to the Golgi complex, perinuclear membrane, and nucleus.
  • Myosin VI knockdown impairs p53 activation, compromises Golgi integrity, and increases apoptosis susceptibility upon DNA damage.

Conclusions:

  • Myosin VI is a novel component of the p53-dependent prosurvival pathway.
  • p53 contributes to Golgi complex integrity maintenance through Myosin VI.
  • Myosin VI plays a crucial role in cellular response to DNA damage, ensuring cell survival.

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