New insight into the formation of stress granules

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New insight into the formation of stress granules

Postby whbio » Mar 13 2017 6:04 pm

A study in PLoS Genetics provides clues to the formation and disassembly of stress granules, which are aggregates of proteins and RNA molecules that are produced by the cells in response to environmental stress. Given that stress granules have been implicated with many diseases, the study will have profound applications.

The formation of stress granules is crucial for cell survival under different conditions. Unfortunately, they sometimes can cause negative effects. When inappropriately formed, stress granules may lead to the development of certain types of neurological disease. Additionally, stress granules are contributing to chemotherapy resistance and metastasis of cancer cells. However, the mechanism underlying the formation and disassembly of stress granules is not completely understood. The current study, carried out by researchers from Kristin Baetz from the Ottawa Institute of Systems Biology, advances understanding this mechanism.

The main findings of the study were that certain enzymes regulate the formation of stress granules upon glucose deprivation. In addition, blocking these enzymes could decrease the levels of stress granules. The study will aid drug development for a range of diseases.

Baetz and colleagues used a species of yeast called Saccharomyces cerevisiae to study stress granules. This yeast species is well studied and has been developed as a model organism in biological research as it has several advantages. For example, yeast cells have many things in common with human cells. The researchers found that the lysine acetyltransferase complex NuA4 is required for stress granule formation upon glucose deprivation but not heat stress. In addition, the metabolite acetyl-CoA is also implicated in this process.

To see whether the findings could apply to mammalian cells, the researchers examined stress granules in human cancer cell lines: HeLa and MCF7. Results confirmed that the mammalian homolog of the NuA4 complex -- the Tip60 complex – indeed contributes to stress granule dynamics.

There is a group of drugs that target NuA4, Tip60, or related enzymes. The researchers said that “there is the possibility that these drugs may reduce stress granule formation offering a novel therapeutic approach to treat numerous diseases.” In addition, Tip60, NuA4, and related antibodies can be offered by Cusabio.
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