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Updated: Mar 29, 2026
Live Cell Imaging of Chromosome Segregation During Mitosis
Published on: March 14, 2018
ASPP1/2-PP1 complexes are required for chromosome segregation and kinetochore-microtubule attachments
Pingzhao Zhang1,2, Yuanyuan Zhang1, Kun Gao1
1State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, P.R. China.
Abstract:
Regulated interactions between kinetochores and spindle microtubules are critical for maintaining genomic stability during chromosome segregation. Defects in chromosome segregation are widespread phenomenon in human cancers that are thought to serve as the fuel for tumorigenic progression. Tumor suppressor proteins ASPP1 and ASPP2, two members of the apoptosis stimulating proteins of p53 (ASPP) family, are frequently down-regulated in human cancers. Here we report that ASPP1/2 are required for proper mitotic progression. In ASPP1/2 co-depleted cells, the persistence of unaligned chromosomes and the reduction of tension across sister kinetochores on aligned chromosomes resulted in persistent spindle assembly checkpoint (SAC) activation. Using protein affinity purification methods, we searched for functional partners of ASPP1/2, and found that ASPP1/2 were associated with a subset of kinetochore proteins (Hec1, KNL-1, and CENP-F). It was found that ASPP1/2 act as PP1-targeting subunits to facilitate the interaction between PP1 and Hec1, and catalyze Hec1 (Ser165) dephosphorylation during late mitosis. These observations revealed a previously unrecognized function of ASPP1/2 in chromosome segregation and kinetochore-microtubule attachments that likely contributes to their roles in chromosome stability and tumor suppression.
Insights
The apoptosis stimulating proteins of p53 (ASPP1/2) are crucial for proper cell division and genomic stability. These tumor suppressors regulate kinetochore-microtubule attachments, preventing cancer progression.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Kinetochore-microtubule interactions are vital for accurate chromosome segregation and genomic stability.
- Defects in chromosome segregation are hallmarks of human cancers.
- ASPP1 and ASPP2, tumor suppressors, are often downregulated in cancers.
Purpose of the Study:
- To investigate the role of ASPP1 and ASPP2 in mitotic progression and chromosome segregation.
- To identify functional partners of ASPP1/2 at the kinetochore.
- To elucidate the mechanism by which ASPP1/2 regulate kinetochore function.
Main Methods:
- Depletion of ASPP1/2 in cells.
- Analysis of chromosome alignment and kinetochore-microtubule attachments.
- Protein affinity purification to identify ASPP1/2 interacting partners.
- Western blotting to assess Hec1 phosphorylation status.
Main Results:
- ASPP1/2 depletion caused chromosome misalignment and reduced kinetochore tension, leading to spindle assembly checkpoint activation.
- ASPP1/2 were found to associate with kinetochore proteins Hec1, KNL-1, and CENP-F.
- ASPP1/2 function as PP1-targeting subunits, promoting Hec1 dephosphorylation at Ser165 during late mitosis.
Conclusions:
- ASPP1/2 play a previously unrecognized role in regulating chromosome segregation through kinetochore-microtubule attachments.
- This function of ASPP1/2 contributes to maintaining genomic stability and their tumor-suppressive activities.
- Dysregulation of ASPP1/2 impacts mitotic fidelity and may promote tumorigenesis.
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