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PIGN 时空调节白血病转化和进展中的纺锤体组装检查点蛋白。

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

机构信息

Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA, USA.

Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Sci Rep. 2021 Sep 24;11(1):19022. doi: 10.1038/s41598-021-98218-y.

DOI:10.1038/s41598-021-98218-y
PMID:34561473
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8463542/
Abstract

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.

摘要

磷脂酰肌醇聚糖锚生物合成类 N（PIGN）与染色体不稳定性的抑制有关。纺锤体组装检查点复合物负责有丝分裂过程中正确的染色体分离，以防止染色体不稳定性。在这项研究中，揭示了 PIGN 作为纺锤体组装检查点调节剂在白血病患者细胞和细胞系中的新作用。瞬时下调或敲除 PIGN 会导致有丝分裂检查点激活受损，这是由于纺锤体组装检查点相关蛋白（包括 MAD1、MAD2、BUBR1 和 MPS1）的表达失调所致。此外，PIGN 的异位过表达恢复了 MAD2 的表达。PIGN 通过与纺锤体组装检查点蛋白 MAD1、MAD2 和有丝分裂激酶 MPS1 形成复合物来调节纺锤体组装检查点。因此，PIGN 可以在纺锤体组装检查点中发挥重要作用，以抑制与白血病转化和进展相关的染色体不稳定性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324b/8463542/3530e1cbdfb3/41598_2021_98218_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324b/8463542/5da6d6f7fc84/41598_2021_98218_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324b/8463542/336a3ea19ccb/41598_2021_98218_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324b/8463542/20dfecc35a66/41598_2021_98218_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324b/8463542/720c9189b579/41598_2021_98218_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324b/8463542/9ddfc2ff1035/41598_2021_98218_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324b/8463542/3530e1cbdfb3/41598_2021_98218_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324b/8463542/5da6d6f7fc84/41598_2021_98218_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324b/8463542/336a3ea19ccb/41598_2021_98218_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324b/8463542/20dfecc35a66/41598_2021_98218_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324b/8463542/720c9189b579/41598_2021_98218_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324b/8463542/9ddfc2ff1035/41598_2021_98218_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324b/8463542/3530e1cbdfb3/41598_2021_98218_Fig6_HTML.jpg

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PLoS One. 2018 Jan 25;13(1):e0191734. doi: 10.1371/journal.pone.0191734. eCollection 2018.
3
Hypotonia and intellectual disability without dysmorphic features in a patient with PIGN-related disease.
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4
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