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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.
The Journal of Cell Biology
|October 27, 2021
Summary
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.
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.
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