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Contribution of caspase(s) to the cell cycle regulation at mitotic phase

Toshiaki Hashimoto1, Ushio Kikkawa, Shinji Kamada

  • 1Biosignal Research Center, Kobe University, Nada-ku, Kobe, Japan.

Plos One
|April 12, 2011
PubMed

Insights

Caspase activity is crucial for cell cycle progression, particularly during mitosis. Inhibiting caspases, especially caspase-3 and -7, halts cell proliferation by causing arrest at the G2/M phase.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Caspases are key regulators of apoptosis but may also influence non-apoptotic cellular processes.
  • Previous research indicated caspase-7's role in cell cycle progression during mitosis.

Purpose of the Study:

  • To investigate the role of caspases in cell cycle regulation beyond apoptosis.
  • To determine which specific caspases are involved in cell proliferation and cell cycle progression.

Main Methods:

  • Utilized broad-spectrum and subtype-specific caspase inhibitors (peptide-based).
  • Employed small interfering RNAs and short hairpin RNA for gene knockdown.
  • Performed flow cytometry and utilized HeLa.S-Fucci cells for cell cycle analysis.
  • Assessed the activity of the Anaphase-Promoting Complex/Cyclosome (APC/C).

Main Results:

  • Broad-spectrum caspase inhibitors and specific inhibitors for caspase-3/-7 dose-dependently inhibited cell proliferation.
  • Inhibitors targeting caspase-3/-7, but not caspase-9, blocked cell proliferation.
  • The BIR2 domain of XIAP (inhibiting caspase-3/-7) induced cell cycle arrest, unlike the BIR3 domain (caspase-9 inhibitor).
  • Caspase inhibition led to G2/M phase arrest and impaired APC/C activity at the M to G1 transition.

Conclusions:

  • Caspases, particularly caspase-3 and -7, play a significant role in regulating the cell cycle at the mitotic phase.
  • Caspase activity is essential for proper cell proliferation and timely progression through mitosis.

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