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DNA-PKcs Negatively Regulates Cyclin B1 Protein Stability through Facilitating Its Ubiquitination Mediated by

Zeng-Fu Shang1, Wei Tan2, Xiao-Dan Liu3

  • 11. School of Radiation Medicine and Protection, Medical College of Soochow University; Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu 215123, P. R. China ; 2. Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology (BKLRB), Beijing Institute of Radiation Medicine, Beijing 100850, P. R. China.

International Journal of Biological Sciences
|July 30, 2015
PubMed

Insights

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) regulates cell division by controlling Cyclin B1 protein stability. Loss of DNA-PKcs leads to abnormal Cyclin B1 accumulation, impacting mitotic progression.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is crucial for DNA repair.
  • Emerging evidence suggests DNA-PKcs also plays a role in mitotic regulation.
  • Cyclin B1 is a key regulator of cell cycle progression, particularly mitosis.

Purpose of the Study:

  • To investigate the role of DNA-PKcs in the regulation of Cyclin B1 protein stability.
  • To elucidate the mechanism by which DNA-PKcs affects Cyclin B1 degradation.
  • To understand the implications of DNA-PKcs in mitotic progression.

Main Methods:

  • Western blotting to assess protein levels.
  • Ubiquitination assays to measure protein modification.
  • Co-immunoprecipitation to study protein interactions.
  • Cell cycle analysis.

Main Results:

  • DNA-PKcs negatively regulates Cyclin B1 stability by promoting its ubiquitination via the Cdh1/APC/C pathway.
  • Loss of DNA-PKcs results in Cyclin B1 accumulation due to delayed degradation.
  • DNA-PKcs kinase activity is essential for its effect on Cyclin B1 stability.
  • DNA-PKcs interacts with APC2 and Cdh1, and its absence accelerates Cdh1 destruction.

Conclusions:

  • DNA-PKcs regulates mitotic progression by controlling Cyclin B1 stability.
  • The mechanism involves facilitating Cyclin B1 ubiquitination and degradation through the Cdh1/APC/C complex.
  • DNA-PKcs has a dual role in DNA repair and cell cycle regulation.
Keywords:
Cyclin B1DNA-PKcs

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