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The STARD9/Kif16a kinesin associates with mitotic microtubules and regulates spindle pole assembly

Jorge Z Torres1, Matthew K Summers, David Peterson

  • 1Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA. torres@chem.ucla.edu

Cell
|December 14, 2011
PubMed

Insights

Researchers identified STARD9, a protein crucial for mitotic spindle assembly. Depleting STARD9 in cancer cells triggers mitotic arrest and apoptosis, suggesting STARD9 as a potential target for cancer therapies.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Cancer Therapeutics

Background:

  • The mitotic spindle is essential for accurate chromosome segregation during cell division.
  • Cancer cells often exhibit aberrant mitotic spindles, making them targets for antimitotic therapies.
  • Identifying novel proteins regulating spindle assembly is key to developing new cancer treatments.

Purpose of the Study:

  • To identify and characterize proteins essential for mitotic spindle assembly.
  • To discover novel regulators of mitosis that could serve as antimitotic drug targets.
  • To investigate the role of STARD9 in spindle formation and its potential as a therapeutic target.

Main Methods:

  • Proteomic and genetic analysis of 592 mitotic microtubule copurifying proteins (MMCPs).
  • Functional characterization of identified proteins, including STARD9, using cell-based assays.
  • Assessment of STARD9's role in spindle assembly, pericentriolar material (PCM) stability, and apoptosis induction.

Main Results:

  • STARD9, a kinesin-3 family member, was identified as a key regulator of spindle assembly.
  • STARD9 localizes to centrosomes and stabilizes the pericentriolar material (PCM).
  • STARD9 depletion leads to PCM fragmentation, multipolar spindle formation, spindle assembly checkpoint (SAC) activation, mitotic arrest, and apoptosis.
  • STARD9 depletion synergizes with taxol, enhancing mitotic cell death.

Conclusions:

  • STARD9 is a critical mitotic kinesin essential for proper spindle assembly and chromosome segregation.
  • STARD9 plays a vital role in maintaining PCM integrity and preventing aberrant spindle formation.
  • STARD9 represents a promising novel antimitotic target for cancer therapy, particularly in combination treatments.

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