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A-kinase anchoring protein 12 regulates the completion of cytokinesis

Moon-Chang Choi1, Yang-Ui Lee, Sung-Hak Kim

  • 1National Research Laboratory for Cancer Epigenetics, Cancer Research Institute, Seoul, Republic of Korea.

Biochemical and Biophysical Research Communications
|June 17, 2008
PubMed

Insights

A-kinase anchoring protein 12 (AKAP12) is crucial for cell division and may act as a tumor suppressor. Its inactivation is linked to gastric cancer, and it plays a role in cytokinesis regulation.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • A-kinase anchoring protein 12 (AKAP12) gene is frequently inactivated in human gastric and other cancers via promoter hypermethylation.
  • The precise biological function of AKAP12 in tumorigenesis is not yet fully understood.
  • Aneuploidy, a common feature of cancer cells, often arises from errors during cell division.

Purpose of the Study:

  • To investigate the biological function of AKAP12 in cancer, particularly its role in cell division and tumorigenesis.
  • To elucidate the mechanism by which AKAP12 influences cell division processes.
  • To determine if AKAP12 functions as a tumor suppressor.

Main Methods:

  • Small interfering RNA (siRNA) was used to deplete AKAP12 expression in cells.
  • Cellular localization of AKAP12 during different cell cycle phases was observed.
  • The effect of AKAP12 depletion on cytokinesis and multinucleation was analyzed.
  • The impact of myosin light chain kinase (MLCK) inhibition on AKAP12 localization was examined.

Main Results:

  • AKAP12 was observed at the cell periphery during interphase and the actomyosin contractile ring during cytokinesis.
  • Depletion of AKAP12 led to an increase in multinucleated cells and impaired cytokinesis completion.
  • Inhibition of MLCK disrupted AKAP12 localization, suggesting AKAP12 is a downstream effector of MLCK.
  • AKAP12 appears to be regulated by MLCK-mediated actomyosin contractility.

Conclusions:

  • AKAP12 plays a significant role in regulating the progression of cytokinesis.
  • These findings suggest a novel tumor suppressor role for AKAP12 in cancer development.
  • AKAP12's function in cell division regulation may be linked to its inactivation in various cancers.

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