Before and after the spindle assembly checkpoint: An APC/C Point of View

The Laboratory of Molecular and Cellular Biology, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, Bethesda, Maryland 20892-0840, USA.
Cell cycle (Georgetown, Tex.) (Impact Factor: 5.01). 10/2006; 5(18):2168-71.
Source: PubMed

ABSTRACT On May 17-21, 2006 the Cold Spring Harbor Laboratory meeting on the cell cycle reunited over 350 researchers to discuss new findings in the cell cycle field. A common thread that connected numerous presentations was the regulation of the anaphase promoting complex/cyclosome (APC/C). This was also the main theme of the lecture given by the keynote speaker, Marc Kirschner (Harvard), who talked about "The unexpected importance of UbcH10 in both the G(1)/S transition and the initiation of anaphase", and it is also the main focus in this summary.

  • [Show abstract] [Hide abstract]
    ABSTRACT: In eukaryotes, the spindle-assembly checkpoint (SAC) is a ubiquitous safety device that ensures the fidelity of chromosome segregation in mitosis. The SAC prevents chromosome mis-segregation and aneuploidy, and its dysfunction is implicated in tumorigenesis. Recent molecular analyses have begun to shed light on the complex interaction of the checkpoint proteins with kinetochores--structures that mediate the binding of spindle microtubules to chromosomes in mitosis. These studies are finally starting to reveal the mechanisms of checkpoint activation and silencing during mitotic progression.
    Nature Reviews Molecular Cell Biology 05/2007; 8(5):379-93. DOI:10.1038/nrm2163 · 36.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: UbcH10 is one of the key regulators of cell cycle progression through the mitotic spindle assembly checkpoint pathway. Recently, aberrantly high UbcH10 expression has been demonstrated in a variety of malignancies. However, its role in astrocytic carcinogenesis is not well defined. This study investigated the splice pattern of the UbcH10 gene and its expression status in astrocytomas of different grades. Consequently, UbcH10 splice variant 1 (GenBank accession nos. NM_007019) was detected in astrocytomas and normal brain tissues by RT-PCR and sequence analysis. Expression levels of UbcH10 mRNA were elevated in high- versus low-grade astrocytomas (64.33+/-60.98 vs 8.36+/-8.15, respectively; p=0.000) or normal controls (64.33+/-60.98 vs 1.00+/-1.57, respectively; p=0.000), as determined by quantitative real time PCR analysis. Similarly, immunohistochemistry study showed increased UbcH10 labelling index in high-grade astrocytomas versus low-grade tumors (10.53+/-5.79% vs 4.23+/-2.85%, respectively; p=0.000) or normal controls (10.53+/-5.79% vs 0.0+/-0.0%, respectively; p=0.000) and, a positive correlation between UbcH10 immunoreactivity and Ki-67 immunostaining was also noted (Spearman r=0.63, p<0.001). These data suggest that overexpression of UbcH10 may serve as one important molecular mechanism that underlies the astrocytic carcinogenesis.
    Brain Research 03/2008; 1201:161-6. DOI:10.1016/j.brainres.2008.01.037 · 2.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The mitotic regulator Aurora-A is an oncogenic protein that is over-expressed in many types of human tumors. However, the underlying mechanism through which Aurora-A promotes tumorigenesis remains unclear. Here, we show that overexpression of Aurora-A causes an elevation of Cyclin B1 expression. Cyclin B1 degradation is delayed in Aurora-A over-expressing cells, which depends on Aurora-A kinase activity. In contrast, Aurora-A RNAi enhances Cyclin B1 degradation. Furthermore, we found that Aurora-A interacts with Cyclin B1, and that Aurora-A overexpression reduces the interaction of Cyclin B1 with APC subunits. In human esophageal squamous cell carcinomas (ESCC), overexpression of Aurora-A was correlated with deregulated expression of Cyclin B1. Taken together, these findings suggest that overexpression of Aurora-A may stabilize Cyclin B1 through inhibiting its degradation. These results provide new insight into the mechanism of how deregulated Aurora-A contributes to genomic instability and carcinogenesis.
    Cancer letters 12/2008; 275(1):77-85. DOI:10.1016/j.canlet.2008.10.011 · 5.62 Impact Factor
Show more