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Serine-Threonine Kinase 38 regulates CDC25A stability and the DNA damage-induced G2/M checkpoint

Takemichi Fukasawa1, Atsushi Enomoto1, Kiyoshi Miyagawa1

  • 1Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Cellular Signalling
|May 5, 2015
PubMed

Insights

DNA damage triggers cell cycle arrest via CDC25A degradation. Serine-threonine kinase 38 (STK38) phosphorylates CDC25A, initiating its degradation and activating the G2/M checkpoint.

Area of Science:

  • Cellular biology
  • Molecular signaling
  • DNA damage response

Background:

  • Cells activate signaling pathways to manage DNA damage, including cell-cycle arrest, repair, or apoptosis.
  • CDC25A (cell division cycle 25 homologue A) phosphatase is crucial for cell-cycle regulation, controlling G1/S and G2/M transitions.
  • DNA damage induces specific degradation of CDC25A, impacting cell-cycle progression.

Purpose of the Study:

  • To investigate the role of serine-threonine kinase 38 (STK38) in the DNA-damage-induced degradation of CDC25A.
  • To elucidate the mechanism by which STK38 regulates CDC25A stability and cell-cycle arrest.

Main Methods:

  • Depletion of STK38 in cells.
  • Analysis of CDC25A degradation and G2 arrest following DNA damage.
  • In vitro phosphorylation assays to identify STK38 targets on CDC25A.

Main Results:

  • Depletion of STK38 inhibited DNA-damage-induced CDC25A degradation and G2 arrest.
  • STK38 was found to directly phosphorylate CDC25A at a specific serine residue (Ser-76).
  • Phosphorylation of CDC25A at Ser-76 by STK38 leads to its degradation.

Conclusions:

  • STK38-mediated phosphorylation of CDC25A at Ser-76 is essential for its degradation.
  • This phosphorylation and subsequent degradation of CDC25A are required for activating the G2/M DNA damage checkpoint.
Keywords:
CDC25ADNA damageDegradationG2/M checkpointSTK38

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