PIGN spatiotemporally regulates the spindle assembly checkpoint proteins in leukemia transformation and progression

被引：4
|
作者：
Teye, Emmanuel K. [1 ]
Lu, Shasha [1 ,2 ]
Chen, Fangyuan [2 ]
Yang, Wenrui [1 ,3 ]
Abraham, Thomas [1 ]
Stairs, Douglas B. [1 ]
Yochum, Gregory S. [1 ]
Brodsky, Robert A. [4 ]
Pu, Jefrey J. [1 ,5 ]
机构：
[1] Penn State Univ, Coll Med, Penn State Canc Inst, Hershey, PA 17033 USA
[2] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Shanghai, Peoples R China
[3] Peking Union Med Coll, Inst Hematol, Tianjin, Peoples R China
[4] Johns Hopkins Med, Div Hematol, Baltimore, MD USA
[5] Univ Arizona, Canc Ctr, 1515 N Campbell Ave,1968C, Tucson, AZ 85724 USA
来源：
SCIENTIFIC REPORTS | 2021年 / 11卷 / 01期
关键词：
MITOTIC CHECKPOINT; MYELODYSPLASTIC SYNDROMES; CHROMOSOMAL INSTABILITY; CONGENITAL-ANOMALIES; GENOMIC INSTABILITY; MAD1; CANCER; BUBR1; KINETOCHORES; REPLICATION;
D O I：
10.1038/s41598-021-98218-y
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Phosphatidylinositol glycan anchor biosynthesis class N (PIGN) has been linked to the suppression of chromosomal instability. The spindle assembly checkpoint complex is responsible for proper chromosome segregation during mitosis to prevent chromosomal instability. In this study, the novel role of PIGN as a regulator of the spindle assembly checkpoint was unveiled in leukemic patient cells and cell lines. Transient downregulation or ablation of PIGN resulted in impaired mitotic checkpoint activation due to the dysregulated expression of spindle assembly checkpoint-related proteins including MAD1, MAD2, BUBR1, and MPS1. Moreover, ectopic overexpression of PIGN restored the expression of MAD2. PIGN regulated the spindle assembly checkpoint by forming a complex with the spindle assembly checkpoint proteins MAD1, MAD2, and the mitotic kinase MPS1. Thus, PIGN could play a vital role in the spindle assembly checkpoint to suppress chromosomal instability associated with leukemic transformation and progression.
引用
收藏
页数：13
相关论文
共 50 条
  • [31] Zw10 is a spindle assembly checkpoint protein that regulates meiotic maturation in mouse oocytes
    Park, Yuram
    Kim, Jae-Sung
    Oh, Jeong Su
    HISTOCHEMISTRY AND CELL BIOLOGY, 2019, 152 (03) : 207 - 215
  • [32] Drosophila checkpoint kinase 2 regulates centrosome function and spindle assembly in response to genotoxic stress
    Takada, S
    Kelkar, A
    Brodsky, M
    Theurkauf, W
    MOLECULAR BIOLOGY OF THE CELL, 2002, 13 : 51A - 51A
  • [33] PCH-2 (TRIP13) regulates the spindle assembly checkpoint strength.
    Defachelles, L.
    Russo, A.
    Nelson, C.
    Bhalla, N.
    MOLECULAR BIOLOGY OF THE CELL, 2018, 29 (26)
  • [34] TAp73 regulates the spindle assembly checkpoint by modulating BubR1 activity
    Tomasini, Richard
    Tsuchihara, Katsuya
    Tsuda, Chiharu
    Lau, Suzanne K.
    Wilhelm, Margareta
    Ruffini, Alessandro
    Tsao, Ming-Sound
    Iovanna, Juan L.
    Jurisicova, Andrea
    Melino, Gerry
    Mak, Tak W.
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (03) : 797 - 802
  • [35] Zw10 is a spindle assembly checkpoint protein that regulates meiotic maturation in mouse oocytes
    Yuram Park
    Jae-Sung Kim
    Jeong Su Oh
    Histochemistry and Cell Biology, 2019, 152 : 207 - 215
  • [36] Maternal-Restraint Stress Increases Oocyte Aneuploidy by Impairing Metaphase I Spindle Assembly and Reducing Spindle Assembly Checkpoint Proteins in Mice
    Zhou, Ping
    Lian, Hua-Yu
    Cui, Wei
    Wei, De-Li
    Li, Qing
    Liu, Yu-Xiang
    Liu, Xin-Yong
    Tan, Jing-He
    BIOLOGY OF REPRODUCTION, 2012, 86 (03)
  • [37] Casein kinase 2 modulates the spindle assembly checkpoint to orchestrate porcine oocyte meiotic progression
    Xiayan ShiYang
    Yilong Miao
    Zhaokang Cui
    Yajuan Lu
    Changyin Zhou
    Yu Zhang
    Bo Xiong
    Journal of Animal Science and Biotechnology, 11
  • [38] Casein kinase 2 modulates the spindle assembly checkpoint to orchestrate porcine oocyte meiotic progression
    ShiYang Xiayan
    Miao Yilong
    Cui Zhaokang
    Lu Yajuan
    Zhou Changyin
    Zhang Yu
    Xiong Bo
    JOURNAL OF ANIMAL SCIENCE AND BIOTECHNOLOGY, 2020, 11 (01)
  • [39] Casein kinase 2 modulates the spindle assembly checkpoint to orchestrate porcine oocyte meiotic progression
    Xiayan Shi Yang
    Yilong Miao
    Zhaokang Cui
    Yajuan Lu
    Changyin Zhou
    Yu Zhang
    Bo Xiong
    JournalofAnimalScienceandBiotechnology, 2020, 11 (03) : 715 - 723
  • [40] WAPL orchestrates porcine oocyte meiotic progression via control of spindle assembly checkpoint activity
    Changyin Zhou
    Yilong Miao
    Xue Zhang
    Bo Xiong
    Reproductive Biology and Endocrinology, 19
12345