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Cell cycle regulation of Greatwall kinase nuclear localization facilitates mitotic progression

Peng Wang1, Jacob A Galan, Karine Normandin

  • 1Institut de recherche en immunologie et en cancérologie, Université de Montréal, Montréal, Québec H3C 3J7, Canada.

The Journal of Cell Biology
|July 17, 2013
PubMed

Insights

Greatwall (Gwl) kinase regulation involves its movement from the nucleus to the cytoplasm during cell division. Polo kinase and cyclin B-Cdk1 control Gwl localization, essential for the mitotic switch.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cell division relies on precise regulation of protein kinases and phosphatases.
  • Greatwall (Gwl) kinase inactivates PP2A-B55 at mitotic entry, but its own regulation is unclear.

Purpose of the Study:

  • To investigate the cell cycle-dependent regulation of Greatwall (Gwl) kinase localization.
  • To identify the mechanisms controlling Gwl's subcellular localization during mitosis.

Main Methods:

  • Studied Gwl localization in Drosophila cells throughout the cell cycle.
  • Identified nuclear localization signals (NLS) within the Gwl protein.
  • Investigated the roles of Polo kinase and cyclin B-Cdk1 in Gwl regulation.

Main Results:

  • Gwl translocates from the nucleus to the cytoplasm during prophase.
  • Two NLS in Gwl's central region are crucial for its function.
  • Polo kinase phosphorylates Gwl, promoting 14-3-3ε binding and cytoplasmic localization.
  • Cyclin B-Cdk1 also contributes to Gwl's nuclear exclusion via a separate mechanism.

Conclusions:

  • Nucleo-cytoplasmic shuttling of Gwl is essential for its in vivo function.
  • Spatial regulation of Gwl at mitotic entry is critical for the "mitotic switch" process.

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