Quality control mechanism closes the protein production ‘on-ramps’ in cells

Quality control mechanism closes the protein production 'on-ramps'
An illustration of stalled ribosomes as stalled cars on a freeway. New work shows that factors GIGYF2 and 4EHP prevent translation from being initiated on problematic messenger RNA fragments. This is akin to closing an on-ramp to prevent additional traffic backups after an incident. Credit: Kamena Kostova and Navid Marvi.

Recent work led by Carnegie’s Kamena Kostova revealed a new quality control system in the protein production assembly line with possible implications for understanding neurogenerative disease.

The DNA that comprises the chromosomes housed in each cell’s nucleus encodes the recipes for how to make proteins, which are responsible for the majority of the physiological actions that sustain life. Individual recipes are transcribed using messenger RNA, which carries this piece of code to a piece of cellular machinery called the ribosome. The ribosome translates the message into amino acids—the building blocks of proteins.

But sometimes messages get garbled. The resulting incomplete

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Substance with new mechanism of action found — ScienceDaily

The villain in this drama has a pretty name: Aurora — Latin for dawn. In the world of biochemistry, however, Aurora (more precisely: Aurora-A kinase) stands for a protein that causes extensive damage. There, it has been known for a long time that Aurora often causes cancer. It triggers the development of leukemias and many pediatric cancers, such as neuroblastomas.

Researchers at the universities of Würzburg and Frankfurt have now developed a drug that can disarm Aurora. Dr. Elmar Wolf, biochemist and research group leader at the Biocenter of Julius-Maximilians-Universität Würzburg (JMU), and Stefan Knapp, Professor of Pharmaceutical Chemistry at Goethe University Frankfurt, have played a leading role in this development. The results of their work have now been published in the latest issue of Nature Chemical Biology.

Making tumor-promoting proteins disappear

“Cancers are usually triggered by tumorigenic proteins,” explains Elmar Wolf. Because cancer cells produce more of these

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Key control mechanism allows cells to form tissues and anatomical structures in the developing embryo

Sticking together
Determination of neural progenitor cell-cell de-adhesion forces using micropipette aspiration. Credit: IST Austria

Under a microscope, the first few hours of every multicellular organism’s life seem incongruously chaotic. After fertilization, a once tranquil single-celled egg divides again and again, quickly becoming a visually tumultuous mosh pit of cells jockeying for position inside the rapidly growing embryo.

Yet, amid this apparent pandemonium, cells begin to self-organize. Soon, spatial patterns emerge, serving as the foundation for the construction of tissues, organs and elaborate anatomical structures from brains to toes and everything in between. For decades, scientists have intensively studied this process, called morphogenesis, but it remains in many ways enigmatic.

Now, researchers at Harvard Medical School and the Institute of Science and Technology (IST) Austria have discovered a key control mechanism that cells use to self-organize in early embryonic development. The findings, published in Science on Oct. 2, shed light on a

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