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

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...

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Autores principales: Emmanuel K. Teye, Shasha Lu, Fangyuan Chen, Wenrui Yang, Thomas Abraham, Douglas B. Stairs, Hong-Gang Wang, Gregory S. Yochum, Robert A. Brodsky, Jeffrey J. Pu
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/de2cadc6ed4e4474b1a7633bdd7d1cd8
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spelling oai:doaj.org-article:de2cadc6ed4e4474b1a7633bdd7d1cd82021-12-02T15:14:48ZPIGN spatiotemporally regulates the spindle assembly checkpoint proteins in leukemia transformation and progression10.1038/s41598-021-98218-y2045-2322https://doaj.org/article/de2cadc6ed4e4474b1a7633bdd7d1cd82021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98218-yhttps://doaj.org/toc/2045-2322Abstract 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.Emmanuel K. TeyeShasha LuFangyuan ChenWenrui YangThomas AbrahamDouglas B. StairsHong-Gang WangGregory S. YochumRobert A. BrodskyJeffrey J. PuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Emmanuel K. Teye
Shasha Lu
Fangyuan Chen
Wenrui Yang
Thomas Abraham
Douglas B. Stairs
Hong-Gang Wang
Gregory S. Yochum
Robert A. Brodsky
Jeffrey J. Pu
PIGN spatiotemporally regulates the spindle assembly checkpoint proteins in leukemia transformation and progression
description 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.
format article
author Emmanuel K. Teye
Shasha Lu
Fangyuan Chen
Wenrui Yang
Thomas Abraham
Douglas B. Stairs
Hong-Gang Wang
Gregory S. Yochum
Robert A. Brodsky
Jeffrey J. Pu
author_facet Emmanuel K. Teye
Shasha Lu
Fangyuan Chen
Wenrui Yang
Thomas Abraham
Douglas B. Stairs
Hong-Gang Wang
Gregory S. Yochum
Robert A. Brodsky
Jeffrey J. Pu
author_sort Emmanuel K. Teye
title PIGN spatiotemporally regulates the spindle assembly checkpoint proteins in leukemia transformation and progression
title_short PIGN spatiotemporally regulates the spindle assembly checkpoint proteins in leukemia transformation and progression
title_full PIGN spatiotemporally regulates the spindle assembly checkpoint proteins in leukemia transformation and progression
title_fullStr PIGN spatiotemporally regulates the spindle assembly checkpoint proteins in leukemia transformation and progression
title_full_unstemmed PIGN spatiotemporally regulates the spindle assembly checkpoint proteins in leukemia transformation and progression
title_sort pign spatiotemporally regulates the spindle assembly checkpoint proteins in leukemia transformation and progression
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/de2cadc6ed4e4474b1a7633bdd7d1cd8
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