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Possible explanation for human diseases caused by defective ribosomes
Date:3/31/2014

Cell Biology and Molecular Genetics at the University of Maryland. "Imagine a scenario where the only supplier of a specific part produces a defective one. If the inspectors do their jobs, very few new cars will reach the market. This scenario would put most car companies out of businessthis is equivalent to bone marrow failure. In the meantime, the demand for new cars increases. This opens the door for an unscrupulous company to fire their inspectors and flood the market with 'lemons.' While good for the company's bottom line in the short term, in the long term the increased rates of accidents and lawsuits wreak havoc."

Dinman collaborated on this study with Kim De Keersmaecker of the University of Leuven in Belgium; Arlen Johnson of the University of Texas at Austin; and Sergey Sulima, who conducted this research as a graduate student in the Department of Cell Biology and Molecular Genetics at UMD and is now a postdoctoral researcher in De Keersmaecker's lab.

The researchers set out to investigate structural, biochemical and other defects in ribosomes that may lead to cancer. The team selected budding yeast as their model system, as assembly of its ribosomes shares many characteristics with human cells, making it a powerful experimental tool. They used a strain of yeast containing a specific ribosomal protein mutation previously identified in patients with a potentially fast-moving form of leukemia known as T-cell acute lymphoblastic leukemia (T-ALL).

When the researchers grew the mutant yeast cells on a petri dish, the cells grew very slowly. The researchers suggest that because of the cells' built-in quality control process, the majority of defective ribosomes carrying the T-ALL mutation do not pass the inspection. This severely limits the supply of ribosomes available to produce proteins, only providing enough ribosomes for cells to barely survive. This supply-and-demand problem hits rapidly dividing cells like blood cells particular
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Contact: Heather Dewar
hdewar@umd.edu
301-405-9267
University of Maryland
Source:Eurekalert  

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