ASPP1/2-PP1 complexes are required for chromosome segregation and kinetochore-microtubule attachments

Pingzhao Zhang, Yuanyuan Zhang, Kun Gao, Yuqi Wang, Xiaofeng Jin, Youheng Wei, Heige Saiyin, Dejie Wang, Jintao Peng, Jian Ma, Yan Tang, Reziya Wumaier, Hongxiu Yu, Yimin Dong, Haojie Huang, Long Yu, Chenji Wang

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)41550-41565
Number of pages16
JournalOncotarget
Volume6
Issue number39
DOIs
StatePublished - Dec 8 2015

Keywords

  • Chromosome Section
  • chromosome segregation
  • dephosphorylation
  • kinetochore-microtubule attachment
  • protein phosphatase 1
  • spindle assembly checkpoint

ASJC Scopus subject areas

  • Oncology

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    Zhang, P., Zhang, Y., Gao, K., Wang, Y., Jin, X., Wei, Y., Saiyin, H., Wang, D., Peng, J., Ma, J., Tang, Y., Wumaier, R., Yu, H., Dong, Y., Huang, H., Yu, L., & Wang, C. (2015). ASPP1/2-PP1 complexes are required for chromosome segregation and kinetochore-microtubule attachments. Oncotarget, 6(39), 41550-41565. https://doi.org/10.18632/oncotarget.6355