scholarly journals Folate deficiency induces mitotic aberrations and chromosomal instability by compromising the spindle assembly checkpoint in cultured human colon cells

Mutagenesis ◽  
2017 ◽  
Vol 32 (6) ◽  
pp. 547-560 ◽  
Author(s):  
Xihan Guo ◽  
Juan Ni ◽  
Yuqian Zhu ◽  
Tao Zhou ◽  
Xiaoling Ma ◽  
...  
Keyword(s):  
Chromosomal Instability ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Human Colon ◽  
Folate Deficiency ◽  
Colon Cells

scholarly journals Spindle assembly checkpoint defects and chromosomal instability in head and neck squamous cell carcinoma

2003 ◽  
Vol 107 (1) ◽  
pp. 46-52 ◽  
Author(s):  
Khalid M. Minhas ◽  
Bhuvanesh Singh ◽  
Wei-wen Jiang ◽  
David Sidransky ◽  
Joseph A. Califano
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Chromosomal Instability ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Neck Squamous Cell Carcinoma

scholarly journals Spindle Assembly Checkpoint Protein Cdc20 Transcriptionally Activates Expression of Ubiquitin Carrier Protein UbcH10

2011 ◽  
Vol 286 (18) ◽  
pp. 15666-15677 ◽  
Author(s):  
Somsubhra Nath ◽  
Taraswi Banerjee ◽  
Debrup Sen ◽  
Tania Das ◽  
Susanta Roychoudhury
Keyword(s):  
Chromosomal Instability ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Regulatory Function ◽  
Physical Interaction ◽  
Anaphase Promoting Complex ◽  
Transcriptional Regulatory ◽  
Subsequent Degradation ◽  
Ubiquitin Conjugating Enzyme ◽  
Wd40 Domain

The spindle assembly checkpoint (SAC) ensures accurate segregation of chromosomes by monitoring kinetochore attachment of spindles during mitosis. Proper progression of mitosis depends on orderly ubiquitination and subsequent degradation of various mitotic inhibitors. At the molecular level, upon removal of SAC, Cdc20 activates E3 ubiquitin ligase anaphase-promoting complex/cyclosome that, along with E2 ubiquitin-conjugating enzyme UbcH10, executes this function. Both Cdc20 and UbcH10 are overexpressed in many cancer types and are associated with defective SAC function leading to chromosomal instability. The precise mechanism of correlated overexpression of these two proteins remains elusive. We show that Cdc20 transcriptionally up-regulates UbcH10 expression. The WD40 domain of Cdc20 is required for this activity. Physical interaction between Cdc20 and anaphase-promoting complex/cyclosome-CBP/p300 complex and its subsequent recruitment to the UBCH10 promoter are involved in this transactivation process. This transcriptional regulatory function of Cdc20 was observed to be cell cycle-specific. We hypothesize that this co-regulated overexpression of both proteins contributes to chromosomal instability.

scholarly journals Chromosomal instability and aneuploidy: a conundrum in cancer evolution

2018 ◽  
Vol 1 ◽  
pp. 28-32
Author(s):  
Jasmin Ali
Keyword(s):  
Chromosomal Instability ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Current Understanding ◽  
Cancer Therapies ◽  
Cancer Evolution ◽  
Hallmarks Of Cancer ◽  
Underlying Mechanisms ◽  
Merotelic Attachments

Chromosomal instability (CIN), defined as an increased rate of gain or loss of whole chromosomes, leads to aneuploid cells, which are cells that display an abnormal number of chromosomes. Both CIN and aneuploidy are hallmarks of cancer, yet the underlying mechanisms of CIN and aneuploidy and their impact on tumourigenesis have remained poorly defined. Although multiple mechanisms have been proposed to explain the role of CIN and aneuploidy in tumourigenesis, this review focuses on three principal pathways leading to CIN: spindle assembly checkpoint defects, merotelic attachments, and cohesion defects. Here, we provide a brief overview of the current understanding of the roles of these mechanisms in CIN and aneuploidy. We also present emerging evidence that contradicts the importance of certain mechanisms in cancer evolution. A clearer understanding of these fundamental pathways could prove to be helpful in developing effective cancer therapies.

scholarly journals PIGN Spatiotemporally Regulates the Spindle Assembly Checkpoint Proteins in Myelodysplastic Syndromes

2020 ◽  
Author(s):  
Emmanuel Teye ◽  
Shasha Lu ◽  
Fangyuan Chen ◽  
Wenrui Yang ◽  
Thomas Abraham ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Chromosomal Instability ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Mitotic Checkpoint ◽  
Vital Role ◽  
Checkpoint Activation ◽  
Checkpoint Proteins ◽  
Mitotic Kinase ◽  
Related Proteins

Abstract Phosphatidylinositol glycan anchor biosynthesis class N (PIGN) has been previously 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 the leukemic transformation of myelodysplastic syndromes.

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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Emmanuel K. Teye ◽  
Shasha Lu ◽  
Fangyuan Chen ◽  
Wenrui Yang ◽  
Thomas Abraham ◽  
...  
Keyword(s):  
Chromosomal Instability ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Mitotic Checkpoint ◽  
Vital Role ◽  
The Novel ◽  
Checkpoint Activation ◽  
Checkpoint Proteins ◽  
Mitotic Kinase ◽  
Related Proteins

AbstractPhosphatidylinositol 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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