Protein implicated in tumor growth may protect against neurodegenerative diseases

Cells translate their genetic material at rapid rates with exquisite precision to reproduce, repair damage or even combat disease. But the process can deregulate and give rise to disease. Byproducts of errant processes can build up like gunk in the gears, especially around neurons, breaking down the repair mechanisms and causing further damage and even neurodegenerative disorders such as Alzheimer's disease.

Now, an international research team may have found that a protein implicated in tumor growth may be able to help regulate awry cellular translation and protect against neuronal decay. They published their results on July 13 in the Cell Reports.

"Researchers have begun to understand that age-related neurodegenerative diseases may be caused by slow but steady accumulation of toxic peptide products, which leads to death of neurons, such as beta-amyloid plaques causing Alzheimer's disease," said lead paper author Katsura Asano, professor in Hiroshima University's Graduate School of Integrated Sciences for Life and also in Division of Biology, Kansas State University. "Repeat-associated non-AUG (RAN) translation is one of the mechanisms that generates such toxic products."

When replicating their genetic material, cells look for specifically ordered markers that signal the spot where they should start and end the copy to make a specific protein. The signal is typically "AUG," but RAN translation doesn't need this signal and can begin processing at other points. The problem is that RAN translation can end up copying bits of repeated genetic information that become the toxic buildup that leads to neurodegeneration.

Taking advantage of our knowledge on translation, we examined whether the translational regulatory protein 5MP can suppress RAN translation, which would also suppress the production of the toxic repeat peptide products."

Katsura Asano, Lead Paper Author

In diseased conditions, 5MP is a protein that can potentially transform a healthy cell into a tumor cell. In healthy conditions, 5MP mimics a protein involved in regulating RAN translation. The researchers used electron microscopy and computer-directed modeling to reveal the structure of the preinitiation complex of molecules that assemble prior to RAN translation beginning. They found that 5MP competes with the protein it mimics in human cells and, when it wins, it reduces RAN translation and its toxic byproducts.

To better understand how this finding translates to disease outcomes, the researchers engineered flies with fragile X-associated tremor ataxia syndrome, a neurodegenerative disorder. They found that increasing the levels of 5MP in the affected flies repressed neuronal toxicity and enhanced their lifespan.

"Taken together, these data suggest that modulation of 5MP levels could be a viable therapeutic target by which to selectively reduce RAN translation in repeat expansion disorders," Asano said. "More studies on 5MP and the mechanism of translation can greatly contribute to the understanding and care of neurodegenerative diseases."

Source:
Journal reference:

Singh, C.R., et al. (2021) Human oncoprotein 5MP suppresses general and repeat-associated non-AUG translation via eIF3 by a common mechanism. Cell Reports. doi.org/10.1016/j.celrep.2021.109376.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Sino Biological and BioGeometry Deepen Strategic Cooperation to Empower Protein R&D with Generative AI