TY - JOUR
T1 - ASPP1/2-PP1 complexes are required for chromosome segregation and kinetochore-microtubule attachments
AU - Zhang, Pingzhao
AU - Zhang, Yuanyuan
AU - Gao, Kun
AU - Wang, Yuqi
AU - Jin, Xiaofeng
AU - Wei, Youheng
AU - Saiyin, Heige
AU - Wang, Dejie
AU - Peng, Jintao
AU - Ma, Jian
AU - Tang, Yan
AU - Wumaier, Reziya
AU - Yu, Hongxiu
AU - Dong, Yimin
AU - Huang, Haojie
AU - Yu, Long
AU - Wang, Chenji
PY - 2015/12/8
Y1 - 2015/12/8
N2 - 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.
AB - 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.
KW - Chromosome Section
KW - chromosome segregation
KW - dephosphorylation
KW - kinetochore-microtubule attachment
KW - protein phosphatase 1
KW - spindle assembly checkpoint
UR - http://www.scopus.com/inward/record.url?scp=85021858791&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021858791&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.6355
DO - 10.18632/oncotarget.6355
M3 - Article
C2 - 26595804
AN - SCOPUS:85021858791
SN - 1949-2553
VL - 6
SP - 41550
EP - 41565
JO - Oncotarget
JF - Oncotarget
IS - 39
ER -