September 25, 2014

While taking an awesome cell biology course in college, I was coming to terms with my mother’s recent ovarian cancer diagnosis. The scientist in my head couldn’t shake the curiosity about how my mother’s cells could have betrayed her so royally. This intersection of basic cell biology and cancer kick-started my interest in cell biology research. Today’s image is from a paper showing a role for the ARF tumor suppressor in maintaining chromosomal stability. THIS paper is one of the million billion reasons why basic research is necessary and important. 

The ARF tumor suppressor is mutated or absent in many cancers, and is known to stabilize p53 in response to cellular stress. Other, p53-independent roles for ARF contribute to its role as a tumor suppressor, but are not well understood. A recent paper describes ARF’s function in chromosome segregation during mitosis, via Aurora B regulation. Britigan and colleagues show that loss of ARF results in aneuploidy, or an incorrect number of chromosomes, stemming from chromosome segregation and spindle organization defects. These defects can be rescued through overexpression of the Aurora B kinase, which helps ensure proper kinetochore-spindle interactions and is overexpressed in some cancers. In the images above, ARF-/- cells (right column) show defects throughout mitosis, when compared to normal cells (left). Defects include misaligned chromosomes during metaphase (top, middle rows), and lagging chromosomes during anaphase (bottom).

Britigan, E., Wan, J., Zasadil, L., Ryan, S., & Weaver, B. (2014). The ARF tumor suppressor prevents chromosomal instability and ensures mitotic checkpoint fidelity through regulation of Aurora B Molecular Biology of the Cell, 25 (18), 2761-2773 DOI: 10.1091/mbc.E14-05-0966

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