Genetic Instability of Breast Cancer Cells Induced by Aberrant Expression of hMpS1
Abstract
Precise biochemical pathways have evolved in eukaryotic cells to coordinate the multiple events needed to ensure genomic stability. Fundamental to these biochemical pathways are checkpoints which serve to monitor the integrity of chromosomes and cell cycle progression. Defects in cell cycle checkpoints can result in gene mutations, chromosome damage and aneuploidy, all of which can contribute to tumorigenesis. The mitotic spindle checkpoint monitors spindle microtubule structure, chromosome alignment on the spindle, and chromosome attachment to kinetochores during mitosis. The spindle checkpoint delays the onset of chromosome segregation during anaphase until any defects in the mitotic spindle are corrected. Human and mouse Mpsl homologs (hMpsl/PYT/TTK and mMpsl/Esk) were identified and recently reported to function in spindle checkpoint and centrosome duplication. Our results show that overexpression of hMpsl activates the spindle checkpoint. hMpsl kinase can also autophosphorylate. We hypothesize that the autophosphorylation of hMpsl is linked to its function in spindle checkpoint by activation of apoptosis that follows mitotic arrest. We found that the overexpression of hMpsl also results in mitotic arrest. Based on the results that Mpsl works upstream of the mitotic spindle signaling pathway in yeast and that induction of mitotic arrest results in apoptosis in mammalian system. Thus, hMpsl might act U a upstream signaling of mitotic checkpoint, initiating cascades of events leading to apoptosis upon induction of mitotic checkpoint in mammalian system.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2004
- Accession Number
- ADA437688
Entities
Organizations
- Beth Israel Deaconess Medical Center