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iASPP contributes to cell cortex rigidity, mitotic cell rounding, and spindle positioning.

Aurélie Mangon1, Danièle Salaün1, Mohamed Lala Bouali1

  • 1Centre de Recherche en Cancérologie de Marseille, Institut National de la Santé et de la Recherche Médicale, Institut Paoli-Calmettes, Aix-Marseille Université, Centre National de la Recherche Scientifique, Marseille, France.

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Inhibitor of p53 and PP1 (iASPP) protein helps cancer cells maintain shape during mitosis by increasing cortical rigidity. This ensures proper spindle positioning and chromosome segregation, crucial for preventing errors.

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Area of Science:

  • Cell Biology
  • Cancer Biology
  • Molecular Biology

Background:

  • iASPP protein inhibits p53 pro-apoptotic activity and is overexpressed in tumors.
  • iASPP is a predicted regulatory subunit of the PP1 phosphatase.
  • Microtubule dynamics are regulated by EB1, a microtubule plus-end binding protein.

Purpose of the Study:

  • To investigate the role of iASPP in mitotic cell mechanics and spindle positioning.
  • To identify novel iASPP interacting partners.
  • To understand how iASPP influences cancer cell geometry during mitosis.

Main Methods:

  • Investigated iASPP interaction with EB1 using an SxIP motif.
  • Performed iASPP silencing and mutation experiments.
  • Assessed microtubule capture, spindle positioning, and cell rounding.
  • Identified and studied the role of Myosin-Ic (Myo1c) as an iASPP partner.

Main Results:

  • iASPP directly associates with EB1 via an SxIP motif.
  • iASPP or EB1 binding disruption leads to defective microtubule capture and abnormal spindle positioning.
  • Myosin-Ic (Myo1c) was identified as a novel iASPP binding partner.
  • Knockdown of iASPP or Myo1c impairs cancer cell rounding during mitosis due to reduced cortical stiffness.
  • iASPP enhances cortical rigidity, promoting spherical cell geometry for accurate mitosis.

Conclusions:

  • iASPP plays a critical role in maintaining cancer cell shape during mitosis through interaction with EB1 and Myo1c.
  • iASPP-mediated cortical rigidity is essential for proper mitotic spindle orientation and chromosome segregation.
  • Targeting iASPP could offer a novel strategy for cancer therapy by disrupting mitotic processes.