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.
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页数：13
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