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Updated: Aug 16, 2026

Live Cell Imaging to Assess the Dynamics of Metaphase Timing and Cell Fate Following Mitotic Spindle Perturbations
07:14

Live Cell Imaging to Assess the Dynamics of Metaphase Timing and Cell Fate Following Mitotic Spindle Perturbations

Published on: September 20, 2019

Sil phosphorylation in a Pin1 binding domain affects the duration of the spindle checkpoint

Stefano Campaner1, Philipp Kaldis, Shai Izraeli

  • 1Research Oncology, Amgen, 1201 Amgen Court West, AW1-J4144, Seattle, WA 98119-3105, USA.

Molecular and Cellular Biology
|July 19, 2005
PubMed

Insights

The Sil protein undergoes crucial mitotic phosphorylation, interacting with Pin1 to regulate the spindle checkpoint. Mutations impairing this phosphorylation shorten the checkpoint, affecting cell cycle progression and Cdc2/cyclin B1 activity.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • SIL is an immediate-early gene vital for embryonic development.
  • SIL is linked to T-cell leukemia-associated translocations.
  • SIL protein phosphorylation patterns during the cell cycle are not fully understood.

Purpose of the Study:

  • To investigate the role of SIL protein phosphorylation during mitosis.
  • To determine the functional significance of SIL phosphorylation in cell cycle regulation.
  • To elucidate the interaction between SIL, Pin1, and the spindle assembly checkpoint.

Main Methods:

  • Analysis of SIL protein phosphorylation during mitosis and prometaphase arrest.
  • Site-directed mutagenesis of serine/threonine-proline motifs in SIL.
  • Assessment of Pin1 binding, spindle checkpoint duration, and Cdc2/cyclin B1 activity.
  • RNA interference-mediated downregulation of SIL expression.

Main Results:

  • SIL protein is hyperphosphorylated during mitosis and interacts with Pin1.
  • Mutations at (S/T)P sites disrupt mitotic phosphorylation, reduce Pin1 binding, and shorten spindle checkpoint duration.
  • Impaired SIL phosphorylation leads to premature mitotic exit, reduced Cdc2/cyclin B1 kinase activity, and T161 dephosphorylation on Cdc2.

Conclusions:

  • Mitotic phosphorylation of SIL is essential for its interaction with Pin1 and proper spindle checkpoint function.
  • A specific region of SIL mediates the presentation of Cdc2 activity during spindle checkpoint arrest.
  • Dysregulation of SIL phosphorylation impacts cell cycle control and may contribute to leukemogenesis.

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